Journal articles: 'Biochemical compound'

1

Smith, Thomas, Pei-i. Ho, Kim Yue, Zina Itkin, Damien MacDougall, Mike Paolucci, Adam Hill, and Douglas S. Auld. "Comparison of Compound Administration Methods in Biochemical Assays." Journal of Biomolecular Screening 18, no. 1 (August 17, 2012): 14–25. http://dx.doi.org/10.1177/1087057112455434.

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Compound sample preparation and delivery are the most critical steps in high-throughput screening (HTS) campaigns. Historically, several methods of compound delivery to assays have been used for HTS, including intermediate plates with prediluted compounds, assay-ready plates (ARPs) using either preplated dried compound films or nanoliter DMSO spots of compounds, as well as pin tool–delivered compounds. We and others have observed differences in apparent compound potency depending on the compound delivery method. To quantitatively measure compound potency differences due to the chosen delivery methods, we conducted a controlled study using a validated biochemical luciferase assay and compared potencies when compounds were delivered in either ARPs (using acoustic dispensed nanoliter spots) or by pin tool. Here we compare hit rates, confirmation rates, false-positive rates, and false-negative rates between the two delivery methods using the luciferase assay. We compared polystyrene (PS) and cyclic olefin copolymer (COC) plates using both delivery methods and examined whether ARPs stored at 4 °C were superior to those stored frozen at −20 °C. The data show that the choice of compound delivery method to the assay has an effect on the apparent IC50’s and that pin tool delivery results in more confirmed hits than preplated compounds, resulting in a lower false-negative rate. However, this effect is minimized through the use of COC plates and by obtaining plates in a “just-in-time” mode. Overall, this report provides guidance on using assay-ready compound plates and has affected the way HTS campaigns are using acoustically dispensed plates in our department.

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McShan, D. C. "Towards Inference of a Biochemical Ontology From a Metabolic Database." Comparative and Functional Genomics 6, no. 7-8 (2005): 398–406. http://dx.doi.org/10.1002/cfg.500.

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In order to predict the metabolic fate of an arbitrary compound based solely on structure, it is useful to be able to identify substructural ‘functional groups’ that are biochemically reactive. These functional groups are the substructural elements that can be removed and replaced to transform one compound into another. This problem of identifying functional groups is related to the problem of classifying compounds. The research presented here discusses the state of the art in biochemical databases and how these sources may be applied to the problem of classifying compounds based solely on structure. We describe a biochemical informatics system for processing molecular data and describe how 100 255 compositional (hasA) relationships are inferred between 835 abstractions and 9500 metabolites from the KEGG Ligand database. Specifically, we focus on the identification of amino acids and consider ways in which the inference of biochemical ontologies for metabolites will be improved in the future.

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Smith, Karen M., and Felissa L. Cohen. "Compound Narcolepsy: Development of Biochemical Imbalance." International Journal of Neuroscience 42, no. 3-4 (January 1988): 229–52. http://dx.doi.org/10.3109/00207458808991598.

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Gehan I Kh, Marei, and Abdelgaleil Samir A M. "Antifungal potential and biochemical effects of monoterpenes and phenylpropenes on plant." Plant Protection Science 54, No. 1 (November 24, 2017): 9–16. http://dx.doi.org/10.17221/9/2017-pps.

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To develop new natural fungicides, six monoterpenes and two phenylpropenes were tested for their antifungal activity against eight plant pathogenic fungi. The results of the mycelial growth inhibition assay showed that trans-cinnamaldehyde was the most potent compound against the eight tested fungi with EC50 values ranging between 0.75 and 3.19 mg/l. This compound caused the higher mycelial growth inhibition than carbendazim. Furthermore, (–)-menthone exhibited strong antifungal activity against Alternaria solani (EC50 = 9.31 mg/l), Penicillium digitatum (EC50 = 16.14 mg/l), and Rhizoctonia solani (EC50 = 24.69 mg/l). Likewise, eugenol showed potent antifungal activity against P. digitatum, R. solani, Fusarium solani, and A. solani, whereas EC50 values were less than 30.0 mg/l. In a separate experiment, trans-cinnamaldehyde, p-cymene, eugenol, and (–)-menthone were evaluated for their inhibitory effects on pectin methyl esterase and cellulase. The tested compounds exhibited the pronounced inhibition of enzyme activities with trans-cinnamaldehyde being the most potent inhibitor for both enzymes.

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Sang, Eun Lee, and Soo Suh Yoon. "Biochemical characterization of wastewater by electrolytic respirometer." Water Science and Technology 31, no. 9 (May 1, 1995): 91–100. http://dx.doi.org/10.2166/wst.1995.0348.

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The use of an electrolytic respirometer for characterization of chemical compounds and wastewater was studied. From the BOD curves generated by the respirometer, the first order biokinetic constant (K), ultimate BOD (BODu) and adaptation period were estimated. The estimated ultimate BOD values of the known chemical compounds were very close to the theoretical oxygen demand values. Using K values, the relative biodegradability of the chemicals could be compared while the adaptation period for each compound could vary with the type of seed micro-organisms used. It was found that BOD5 values determined by the conventional method have no or very little, if any, meaning as far as the biological characteristics of industrial wastewaters are concerned. The BOD curves for wastewaters consisting of 2 or 3 different compounds could be divided into several stages while those for the combined wastewaters could be expressed as one curve.

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van Wyk, Niël, Heinrich Kroukamp, and Isak Pretorius. "The Smell of Synthetic Biology: Engineering Strategies for Aroma Compound Production in Yeast." Fermentation 4, no. 3 (July 16, 2018): 54. http://dx.doi.org/10.3390/fermentation4030054.

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Yeast—especially Saccharomyces cerevisiae—have long been a preferred workhorse for the production of numerous recombinant proteins and other metabolites. S. cerevisiae is a noteworthy aroma compound producer and has also been exploited to produce foreign bioflavour compounds. In the past few years, important strides have been made in unlocking the key elements in the biochemical pathways involved in the production of many aroma compounds. The expression of these biochemical pathways in yeast often involves the manipulation of the host strain to direct the flux towards certain precursors needed for the production of the given aroma compound. This review highlights recent advances in the bioengineering of yeast—including S. cerevisiae—to produce aroma compounds and bioflavours. To capitalise on recent advances in synthetic yeast genomics, this review presents yeast as a significant producer of bioflavours in a fresh context and proposes new directions for combining engineering and biology principles to improve the yield of targeted aroma compounds.

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Lagha-Benamrouche, Samira, Terkia Benaissa, and Rezki Sadoudi. "Desamerization of Bitter Jam: Biochemical and Sensory Quality." Journal of Food Quality 2018 (July 29, 2018): 1–13. http://dx.doi.org/10.1155/2018/8178059.

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This work consists of studying the influence of the desamerization of the mesocarpe on the chemical composition and the sensorial quality of the jam, based on the bitter orange. The results of the various analysis show that desamerization decreases acidity, sugars, protein, and bioactive compound levels (carotenoids, polyphenols, and vitamin C), but desamerized jams still remain an important source of antioxidant compounds with antioxidant potential in the diet. Concerning the sensory analysis of the jams, the results show that the jam desamerized with water presents the same bitterness as the bitter jam and that the salt significantly reduces the bitterness of the jams.

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Haskins, J. Thomas, Eric A. Muth, and T. H. Andree. "Biochemical and electrophysiological studies of the psychotropic compound, amperozide." Brain Research Bulletin 19, no. 4 (October 1987): 465–71. http://dx.doi.org/10.1016/0361-9230(87)90151-1.

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Moriev, R., O. Vasylchenko, M. Platonov, O. Grygorenko, K. Volkova, and S. Zozulya. "Identification of Novel IGF1R Kinase Inhibitors by Molecular Modeling and High-Throughput Screening." Acta Naturae 5, no. 2 (June 15, 2013): 90–99. http://dx.doi.org/10.32607/20758251-2013-5-2-90-99.

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The aim of this study was to identify small molecule compounds that inhibit the kinase activity of the IGF1 receptor and represent novel chemical scaffolds, which can be potentially exploited to develop drug candidates that are superior to the existing experimental anti-IGF1R therapeuticals. To this end, targeted compound libraries were produced by virtual screening using molecular modeling and docking strategies, as well as the ligand-based pharmacophore model. High-throughput screening of the resulting compound sets in a biochemical kinase inhibition assay allowed us to identify several novel chemotypes that represent attractive starting points for the development of advanced IGF1R inhibitory compounds.

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Šindelář, Karel, Karel Dobrovský, Ivan Krejčí, and Zdeněk Polívka. "Substituted 1-(2-Thienyl)cyclohexylamines and Related Compounds as Potential NMDA Antagonists." Collection of Czechoslovak Chemical Communications 60, no. 5 (1995): 894–902. http://dx.doi.org/10.1135/cccc19950894.

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Reactions of bisulfite addition compounds prepared in situ from cyclohexanone or 3,4,5,6-tetrahydro-2H-thiopyran-3-one with potassium cyanide and corresponding amines resulted with high yields in amino nitriles type of V and VI. These compounds were subjected to reactions with 2-thienylmagnesium bromide and in the case of the amino nitriles Vc and Vf with 5-bromo-2-thienylmagnesium bromide. Only in the case of compound Vf, a by-product X was isolated in addition to the desired 1-[1-(5-bromo-2-thienyl)-1-cyclohexyl]piperidine (VIIf). Compound VIIf was used for the synthesis of the carboxylic acid XI. The compounds prepared were tested by some methods of biochemical and behavioural pharmacology.

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Mathai, Neann, Conrad Stork, and Johannes Kirchmair. "BonMOLière: Small-Sized Libraries of Readily Purchasable Compounds, Optimized to Produce Genuine Hits in Biological Screens across the Protein Space." International Journal of Molecular Sciences 22, no. 15 (July 21, 2021): 7773. http://dx.doi.org/10.3390/ijms22157773.

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Experimental screening of large sets of compounds against macromolecular targets is a key strategy to identify novel bioactivities. However, large-scale screening requires substantial experimental resources and is time-consuming and challenging. Therefore, small to medium-sized compound libraries with a high chance of producing genuine hits on an arbitrary protein of interest would be of great value to fields related to early drug discovery, in particular biochemical and cell research. Here, we present a computational approach that incorporates drug-likeness, predicted bioactivities, biological space coverage, and target novelty, to generate optimized compound libraries with maximized chances of producing genuine hits for a wide range of proteins. The computational approach evaluates drug-likeness with a set of established rules, predicts bioactivities with a validated, similarity-based approach, and optimizes the composition of small sets of compounds towards maximum target coverage and novelty. We found that, in comparison to the random selection of compounds for a library, our approach generates substantially improved compound sets. Quantified as the “fitness” of compound libraries, the calculated improvements ranged from +60% (for a library of 15,000 compounds) to +184% (for a library of 1000 compounds). The best of the optimized compound libraries prepared in this work are available for download as a dataset bundle (“BonMOLière”).

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12

Rademacher, W., J. B. Speakman, R. R. Evans, J. R. Evans, S. Roemmelt, S. Michalek, A. Lux-Endrich, D. Treutter, T. Iturriagagoitia-Bueno, and P. John. "Prohexadione-Ca—A New Plant Growth Regulator for Apple with Interesting Biochemical Features." HortScience 33, no. 3 (June 1998): 540d—540. http://dx.doi.org/10.21273/hortsci.33.3.540d.

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Prohexadione-Ca is currently developed as an inhibitor of excessive vegetative growth in apple. In addition to the control of shoot growth, distinct effects on the incidence of fireblight are observed that are not due to any bactericidal effect of the compound. Further, the compound often causes a delay of senescence. It is known that prohexadione-Ca acts as a structural mimic of 2-oxoglutarate thereby inhibiting dioxygenases, which catalyze distinct steps in gibberellin (GA) biosynthesis. As a result, levels of growth-active GAs are lowered and, hence, longitudinal shoot growth is reduced. Prohexadione-Ca also induces changes in flavonoid metabolism, which may also be related to the inhibition of dioxygenases involved in this pathway. Preliminary evidence is available that this effect is related to a lowered susceptibility of apple tissue towards infection with fireblight. ACC oxidase, another dioxygenase, which catalyzes the conversion of aminocyclopropane-carboxylic acid into ethylene, is also affected by prohexadione-Ca and related compounds. Lowered levels of ethylene may account for a delay of senescence.

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Fonseca Lameiro, Rafael da, Anwar Shamim, Fabiana Rosini, Rodrigo Cendron, Pedro Henrique Jatai Batista, and Carlos Alberto Montanari. "Synthesis, biochemical evaluation and molecular modeling studies of nonpeptidic nitrile-based fluorinated compounds." Future Medicinal Chemistry 13, no. 1 (January 2021): 25–43. http://dx.doi.org/10.4155/fmc-2020-0057.

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Aim: Compounds that block enzyme activity can kill pathogens and help develop effective and safe drugs for Chagas disease and leishmaniasis. Materials & methods: A library of nonpeptidic nitrile-based compounds was synthesized and had their inhibitory affinity tested against cruzain, Leishmania mexicana cysteine protease B and cathepsin L. Isothermal titration calorimetry experiments and molecular simulations were performed for selected compounds to obtain thermodynamic fingerprints and identify main interactions and putative modes of binding with cruzain. Results: The derivatives provided increased affinity against all enzymes compared with the lead, and thermodynamic and computational studies showed improved thermodynamic properties and a possible different mode of binding. Conclusion: Our studies culminated in 1b, a compound 60-fold more potent in cruzain than its lead that also showed entropic and enthalpic contributions favorable to Gibbs binding energy.

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Ong, L. L., J. D. Vasta, L. Monereau, G. Locke, H. Ribeiro, M. A. Pattoli, S. Skala, et al. "A High-Throughput BRET Cellular Target Engagement Assay Links Biochemical to Cellular Activity for Bruton’s Tyrosine Kinase." SLAS DISCOVERY: Advancing the Science of Drug Discovery 25, no. 2 (November 9, 2019): 176–85. http://dx.doi.org/10.1177/2472555219884881.

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Protein kinases are intensely studied mediators of cellular signaling. While traditional biochemical screens are capable of identifying compounds that modulate kinase activity, these assays are limited in their capability of predicting compound behavior in a cellular environment. Here, we aim to bridge target engagement and compound-cellular phenotypic behavior by utilizing a bioluminescence resonance energy transfer (BRET) assay to characterize target occupancy within living cells for Bruton’s tyrosine kinase (BTK). Using a diverse chemical set of BTK inhibitors, we determine intracellular engagement affinity profiles and successfully correlate these measurements with BTK cellular functional readouts. In addition, we leveraged the kinetic capability of this technology to gain insight into in-cell target residence time and the duration of target engagement, and to explore a structural hypothesis.

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Stokes, Neil R., Helena B. Thomaides-Brears, Stephanie Barker, James M. Bennett, Joanne Berry, Ian Collins, Lloyd G. Czaplewski, et al. "Biological Evaluation of Benzothiazole Ethyl Urea Inhibitors of Bacterial Type II Topoisomerases." Antimicrobial Agents and Chemotherapy 57, no. 12 (September 16, 2013): 5977–86. http://dx.doi.org/10.1128/aac.00719-13.

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ABSTRACTThe type II topoisomerases DNA gyrase (GyrA/GyrB) and topoisomerase IV (ParC/ParE) are well-validated targets for antibacterial drug discovery. Because of their structural and functional homology, these enzymes are amenable to dual targeting by a single ligand. In this study, two novel benzothiazole ethyl urea-based small molecules, designated compound A and compound B, were evaluated for their biochemical, antibacterial, and pharmacokinetic properties. The two compounds inhibited the ATPase activity of GyrB and ParE with 50% inhibitory concentrations of <0.1 μg/ml. Prevention of DNA supercoiling by DNA gyrase was also observed. Both compounds potently inhibited the growth of a range of bacterial organisms, including staphylococci, streptococci, enterococci,Clostridium difficile, and selected Gram-negative respiratory pathogens. MIC90s against clinical isolates ranged from 0.015 μg/ml forStreptococcus pneumoniaeto 0.25 μg/ml forStaphylococcus aureus. No cross-resistance with common drug resistance phenotypes was observed. In addition, no synergistic or antagonistic interactions between compound A or compound B and other antibiotics, including the topoisomerase inhibitors novobiocin and levofloxacin, were detected in checkerboard experiments. The frequencies of spontaneous resistance forS. aureuswere <2.3 × 10−10with compound A and <5.8 × 10−11with compound B at concentrations equivalent to 8× the MICs. These values indicate a multitargeting mechanism of action. The pharmacokinetic properties of both compounds were profiled in rats. Following intravenous administration, compound B showed approximately 3-fold improvement over compound A in terms of both clearance and the area under the concentration-time curve. The measured oral bioavailability of compound B was 47.7%.

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Elo, Hannu, Raija Laine, Leena Alhonen-Hongisto, Juhani Jänne, Ilpo Mutikainen, and Paavo Lumme. "Biochemical Characterization of Propylglyoxal Bis(guanylhydrazone). Facile Synthesis of Monoalkylglyoxal Bis(guanylhydrazones)." Zeitschrift für Naturforschung C 40, no. 11-12 (October 1, 1985): 839–42. http://dx.doi.org/10.1515/znc-1985-11-1214.

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Abstract Propylglyoxal Bis(guanylhydrazone). Ethylglyoxal Bis(guanylhydrazone), Adenosylmethionine Decarboxylase Inhibition. Tumor Cells, Cellular Uptake Propylglyoxal bis(guanylhydrazone) sulfate, a novel analog of the well-known antileukemic drug methylglyoxal bis(guanylhydrazone), has been prepared from 2,2-dibromopentanal, and the compound has been characterized biochemically. Although it is a powerful inhibitor of S-adenosylmethionine decarboxylase, its Ki, value (0.2 μᴍ) is considerably higher than that of ethylglyoxal bis(guanylhydrazone) (0.06 μᴍ). The compound is only poorly taken up by tumor cells, and its accumulation is not stimulated by a prior exposure of the tumor cells to di-fluoromethylornithine, a compound that causes polyamine depletion. Thus, the uptake charac teristics of the compound are similar to those of ethylglyoxal bis(guanylhydrazone), but in striking contrast to those of methylglyoxal and glyoxal bis(guanylhydrazones). Since the configuration of the double bonds in glyoxal, methylglyoxal and propylglyoxal bis(guanylhydrazones) has been shown to be identical, the different uptake characteristics are probably only due to differences in side chain size and/or hydrophobicity.

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Galitz, Adrian, Yoichi Nakao, Peter J. Schupp, Gert Wörheide, and Dirk Erpenbeck. "A Soft Spot for Chemistry–Current Taxonomic and Evolutionary Implications of Sponge Secondary Metabolite Distribution." Marine Drugs 19, no. 8 (August 4, 2021): 448. http://dx.doi.org/10.3390/md19080448.

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Marine sponges are the most prolific marine sources for discovery of novel bioactive compounds. Sponge secondary metabolites are sought-after for their potential in pharmaceutical applications, and in the past, they were also used as taxonomic markers alongside the difficult and homoplasy-prone sponge morphology for species delineation (chemotaxonomy). The understanding of phylogenetic distribution and distinctiveness of metabolites to sponge lineages is pivotal to reveal pathways and evolution of compound production in sponges. This benefits the discovery rate and yield of bioprospecting for novel marine natural products by identifying lineages with high potential of being new sources of valuable sponge compounds. In this review, we summarize the current biochemical data on sponges and compare the metabolite distribution against a sponge phylogeny. We assess compound specificity to lineages, potential convergences, and suitability as diagnostic phylogenetic markers. Our study finds compound distribution corroborating current (molecular) phylogenetic hypotheses, which include yet unaccepted polyphyly of several demosponge orders and families. Likewise, several compounds and compound groups display a high degree of lineage specificity, which suggests homologous biosynthetic pathways among their taxa, which identifies yet unstudied species of this lineage as promising bioprospecting targets.

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Rodríguez Marañón, M. J., D. Mercier, R. B. van Huystee, and M. J. Stillman. "Analysis of the optical absorption and magnetic-circular-dichroism spectra of peanut peroxidase: electronic structure of a peroxidase with biochemical properties similar to those of horseradish peroxidase." Biochemical Journal 301, no. 2 (July 15, 1994): 335–41. http://dx.doi.org/10.1042/bj3010335.

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The electronic structures of the cationic isoenzyme of peanut peroxidase, horseradish peroxidase (isoenzyme C) and bovine liver catalase are compared through analysis of their optical absorption and magnetic c.d. (m.c.d.) spectral properties. The spectral data for the native resting states and compounds I and II of peanut peroxidase (PeP) are reported. The absorption and m.c.d. data for the native PeP exhibit bands characteristic of the high-spin ferric haem. The absorption spectrum of PeP compound I closely resembles that observed for the HRP compound I species. The m.c.d. data for PeP I clearly identifies that ring oxidation has occurred. One-electron reduction forms the PeP compound II species. The absorption and m.c.d. spectra recorded for PeP II exhibit the well-resolved spectral characteristics previously observed for both HRP compound II and catalase compound II. The spectral data of PeP with HRP and catalase are compared. The data clearly indicate that the m.c.d. spectral patterns of both plant peroxidases (PeP and HRP) are very similar and, therefore, the electronic structures of their resting states, and as well their primary and secondary compounds, must be similar. The m.c.d. data suggest that, while the compound I species of PeP and HRP belong to one electronic class, catalase compound I belongs to a different class. These data emphasize how the ground states of these two classes of oxidized haem, may be characterized as predominantly 2A2u (PeP I and HRP I) or 2A1u (catalase I). Peanut peroxidase is the second plant peroxidase for which the electronic structure of the compound I intermediate has been studied using the m.c.d. technique. The similarities with horseradish peroxidase allow us to suggest that plant peroxidases may operate by the same general mechanism, in spite of the low degree of sequence similarity between their polypeptide chains.

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Ibáñez, Glorymar, Paul A. Calder, Constantin Radu, Bhavneet Bhinder, David Shum, Christophe Antczak, and Hakim Djaballah. "Evaluation of Compound Optical Interference in High-Content Screening." SLAS DISCOVERY: Advancing the Science of Drug Discovery 23, no. 4 (May 3, 2017): 321–29. http://dx.doi.org/10.1177/2472555217707725.

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Compound optical interference remains an inherent problem in chemical screening and has been well documented for biochemical assays and less so for automated microscopy-based assays. It has also been the assumption that the latter should not suffer from such interference because of the washing steps involved in the process, thus eliminating the residual nonspecific compound effects. Instead, these compounds may have no relevance to the actual target, and as such, compound optical interference contributes to a number of false-positives, resulting in a high attrition rate during subsequent follow-up studies. In this report, we analyze the outcome of a high-content screen using enhanced green fluorescent protein as a reporter in a gain-of-function cell-based assay in search of modulators of the micro RNA (miRNA) biogenesis pathway. Using a previously validated image-based biosensor, we screened a diverse library collection of ~315,000 compounds covering natural and synthetic derivatives in which 1130 positives were identified to enhance green fluorescence expression. Lateral confirmation and dose-response studies revealed that all of these compounds were the result of optical interference and not specific inhibition of miRNA biogenesis. Here, we highlight the chemical classes that are susceptible to compound optical interference and discuss their implications in automated microscopy-based assays.

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Toziuk, Olena, Olga Krasna, Olena Kryvoviaz, Victoria Rodinkova, Andrii Melnyk, Tanya Ivko, Alona Voronkina, and Viktoriia Hutsol. "Biochemical aspects of KB-28 compound on physically loaded study subjects." Current Issues in Pharmacy and Medical Sciences 32, no. 3 (September 1, 2019): 168–72. http://dx.doi.org/10.2478/cipms-2019-0030.

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Abstract In previous studies of actoprotective activity of 5-R-thio-tetrazolo[1,5]quinazoline derivatives in normal and complicated experimental conditions, sodium 2-(tetrazolo [1,5-c]quinazoline-5-ylthio)acetate (KB-28) was found to be the leader of the experiment. The objective of the current study was to characterize the effects of KB-28 compounds on carbohydrate and lipid exchange indices under the conditions of physical load as a possible mechanism of actoprotective effect. In the course of the experiment, the indices of carbohydrate and lipid exchange in the muscle, blood and liver of animal models were determined following a 15-day physical load course. In doing so, glucose, glycogen and total lipid concentrations were assessed. The KB-28 compound was administered daily at levels determined during the course of regular physical load normalized metabolic processes in rats. The results were then compared to a control which received intraperitoneally the equivolume 0.9% sodium chloride solution. The phenomenon of actoprotection consisted in enhancing concentrations of glycogen in skeletal muscles and liver. Compared to the control figures, this increase was 28.8% and 25.0%, accordingly. Moreover, the course of KB-28 caused a statistically significant reduction (by 32.1%) of the total serum lipid concentration in the animals under physical load. The effect may be a sign of the ability of this substance to utilize active lipolysis for improvement of the skeletal muscle performance. Having analyzed the results obtained, we can draw a conclusion that influencing the biochemical processes in the study models is one of the mechanisms of the KB-28 actoprotective effect.

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Zhang, Haoran, Brian Pereira, Zhengjun Li, and Gregory Stephanopoulos. "Engineering Escherichia coli coculture systems for the production of biochemical products." Proceedings of the National Academy of Sciences 112, no. 27 (June 25, 2015): 8266–71. http://dx.doi.org/10.1073/pnas.1506781112.

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Engineering microbial consortia to express complex biosynthetic pathways efficiently for the production of valuable compounds is a promising approach for metabolic engineering and synthetic biology. Here, we report the design, optimization, and scale-up of an Escherichia coli-E. coli coculture that successfully overcomes fundamental microbial production limitations, such as high-level intermediate secretion and low-efficiency sugar mixture utilization. For the production of the important chemical cis,cis-muconic acid, we show that the coculture approach achieves a production yield of 0.35 g/g from a glucose/xylose mixture, which is significantly higher than reported in previous reports. By efficiently producing another compound, 4-hydroxybenzoic acid, we also demonstrate that the approach is generally applicable for biosynthesis of other important industrial products.

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Mueller, Niklaus H., Nagarajan Pattabiraman, Camilo Ansarah-Sobrinho, Prasanth Viswanathan, Theodore C. Pierson, and R. Padmanabhan. "Identification and Biochemical Characterization of Small-Molecule Inhibitors of West Nile Virus Serine Protease by a High-Throughput Screen." Antimicrobial Agents and Chemotherapy 52, no. 9 (July 7, 2008): 3385–93. http://dx.doi.org/10.1128/aac.01508-07.

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ABSTRACT West Nile virus and dengue virus are mosquito-borne flaviviruses that cause a large number of human infections each year. No vaccines or chemotherapeutics are currently available. These viruses encode a serine protease that is essential for polyprotein processing, a required step in the viral replication cycle. In this study, a high-throughput screening assay for the West Nile virus protease was employed to screen ∼32,000 small-molecule compounds for identification of inhibitors. Lead inhibitor compounds with three distinct core chemical structures (1 to 3) were identified. In a secondary screening of selected compounds, two compounds, belonging to the 8-hydroxyquinoline family (compounds A and B) and containing core structure 1, were identified as potent inhibitors of the West Nile virus protease, with K i values of 3.2 ± 0.3 μM and 3.4 ± 0.6 μM, respectively. These compounds inhibited the dengue virus type 2 protease with K i values of 28.6 ± 5.1 μM and 30.2 ± 8.6 μM, respectively, showing some selectivity in the inhibition of these viral proteases. However, the compounds show no inhibition of cellular serine proteases, trypsin, or factor Xa. Kinetic analysis and molecular docking of compound B onto the known crystal structure of the West Nile virus protease indicate that the inhibitor binds in the substrate-binding cleft. Furthermore, compound B was capable of inhibiting West Nile virus RNA replication in cultured Vero cells (50% effective concentration, 1.4 ± 0.4 μM; selectivity index, 100), presumably by inhibition of polyprotein processing.

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Badawy, M. E. I., S. A. M. Abdelgaleil, T. Suganuma, and M. Fuji. "Antibacterial and biochemical activity of pseudoguaianolide sesquiterpenes isolated from Ambrosia maritima against plant pathogenic bacteria." Plant Protection Science 50, No. 2 (May 6, 2014): 64–69. http://dx.doi.org/10.17221/28/2013-pps.

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Five pseudoguaianolide sesquiterpenes (neoambrosin, damsinic acid, damsin, ambrosin, and hymenin) isolated from the aerial parts of Ambrosia maritima were tested for their antibacterial activity against two plant pathogenic bacteria, Agrobacterium tumefaciens and Erwinia carotovora. The tested compounds exhibited variable degree of antibacterial activity against both tested bacteria as minimum inhibitory concentrations (MIC) ranged 90–520 mg/l. Neoambrosin showed the highest antibacterial activity among the tested sesquiterpenes with MIC values of 150 and 90 mg/l against A. tumefaciens and E. carotovora, respectively. On the contrary, hymenin was the least effective compound with MIC values of 520 and 310 mg/l against A. tumefaciens and E. carotovora, respectively. Neoambrosin, damsinic acid, and damsin caused significant reduction in sulfhydryl group content with the former being the most effective. The tested sesquiterpenes significantly inhibited polygalacturonase and pectin-lyase activities of A. tumefaciens and E. carotovora except for hymenin which caused a significant activation of E. carotovora enzymes.  

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Naz, Sumaira, Muhammad Zahoor, Muhammad Naveed Umar, Saad Alghamdi, Muhammad Umar Khayam Sahibzada, and Wasim UlBari. "Synthesis, characterization, and pharmacological evaluation of thiourea derivatives." Open Chemistry 18, no. 1 (June 29, 2020): 764–77. http://dx.doi.org/10.1515/chem-2020-0139.

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AbstractThioureas and their derivatives are organosulfur compounds having applications in numerous fields such as organic synthesis and pharmaceutical industries. Symmetric thiourea derivatives were synthesized by the reaction of various anilines with CS2. The synthesized compounds were characterized using the UV-visible and nuclear magnetic resonance (NMR) spectroscopic techniques. The compounds were screened for in vitro inhibition of α-amylase, α-glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes and for their antibacterial and antioxidant potentials. These compounds were fed to Swiss male albino mice to evaluate their toxicological effects and potential to inhibit glucose-6-phosphatase (G6Pase) inhibition. The antibacterial studies revealed that compound 4 was more active against the selected bacterial strains. Compound 1 was more active against 2,2-diphenyl-1-picrylhydrazyl and 2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals, AChE, BuChE, and α-glucosidase. Compound 2 was more potent against α-amylase and G6Pase. Toxicity studies showed that compound 4 is safe as it exerted no toxic effect on any of the hematological and biochemical parameters or on liver histology of the experimental animals at any studied dose rate. The synthesized compounds showed promising antibacterial and antioxidant potential and were very active (both in vitro and in vivo) against G6Pase and moderately active against the other selected enzymes used in this study.

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Rees, Robert C., Simon Parker, Andrew Platts, Michael G. Blackburn, and Sheila MacNeil. "Evidence for the involvement of calmodulin in natural cytotoxicity using a range of calmodulin antagonists of varying potency and improved specificity." Bioscience Reports 7, no. 10 (October 1, 1987): 771–75. http://dx.doi.org/10.1007/bf01116749.

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The calmodulin antagonist W7 and 4 of its analogues were examined for their ability to inhibit human NK cell mediated cytotoxicity. With the exception of one of these compounds, which is extremely hydrophobic, there was a good correlation between the ability of drugs to inhibit human NK antitumour cytotoxicity and calmodulin-dependent phosphodiesterase activity in vitro. The most potent of the compounds, 5-iodo-l-C8, an analogue of W7, has an IC50 of 3 μM upon biological and biochemical assay. This particular compound is both more potent and specific than the parent compound W7, is non-toxic to cells over the range used and is also capable of inhibiting the biological activity of NK cells upon pre-treatment of the effector cells, inferring the mechanism of NK cytotoxicity to be calmodulin dependent.

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Gordon, Laurie J., Morven Allen, Per Artursson, Michael M. Hann, Bill J. Leavens, André Mateus, Simon Readshaw, Klara Valko, Gareth J. Wayne, and Andy West. "Direct Measurement of Intracellular Compound Concentration by RapidFire Mass Spectrometry Offers Insights into Cell Permeability." Journal of Biomolecular Screening 21, no. 2 (September 3, 2015): 156–64. http://dx.doi.org/10.1177/1087057115604141.

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One of the key challenges facing early stage drug discovery is understanding the commonly observed difference between the activity of compounds in biochemical assays and cellular assays. Traditionally, indirect or estimated cell permeability measurements such as estimations from logP or artificial membrane permeability are used to explain the differences. The missing link is a direct measurement of intracellular compound concentration in whole cells. This can, in some circumstances, be estimated from the cellular activity, but this may also be problematic if cellular activity is weak or absent. Advances in sensitivity and throughput of analytical techniques have enabled us to develop a high-throughput assay for the measurement of intracellular compound concentration for routine use to support lead optimization. The assay uses a RapidFire-MS based readout of compound concentration in HeLa cells following incubation of cells with test compound. The initial assay validation was performed by ultra-high performance liquid chromatography tandem mass spectrometry, and the assay was subsequently transferred to RapidFire tandem mass spectrometry. Further miniaturization and optimization were performed to streamline the process, increase sample throughput, and reduce cycle time. This optimization has delivered a semi-automated platform with the potential of production scale compound profiling up to 100 compounds per day.

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AL-FARIS, Hussein Dheyaa Hussein, Ibrahim BULDUK, and Ahmet KAHRAMAN. "Biochemical and Micro-morphoanatomical Investigations on Leucojum aestivum L." Notulae Botanicae Horti Agrobotanici Cluj-Napoca 47, no. 4 (December 23, 2019): 1382–93. http://dx.doi.org/10.15835/nbha47411733.

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Leucojum aestivum (snowflake) contains galantamine, a medication used for the treatment of Alzheimer's disease. However, polyphenolic compounds of this species were not studied earlier. Proper understanding of the polyphenolics in the species and their antioxidant properties may lead to a review of their medical use. Therefore, in this study, the polyphenolic content of L. aestivum was determined by UV spectrophotometric and HPLC methods. DPPH, ABTS+, and RPC assays were performed for assessment of its antioxidant potential. Flower and leaf extracts of L. aestivum were found to have more antioxidant activity than its bulbs. This result demonstrated that it was an important source of antioxidant compounds. Qualitative and quantitative findings showed that it contained significant amounts of polyphenols. Naringenin, rosmarinic, p-coumaric, syringic, and gallic acid compounds were identified in the leaf and flower extracts. Methanol extracts of the fowers, leaves and bulbs had no activity against pathogenic bacterial strains. The methanolic flower and leaf extracts showed the most antifungal effective against Alternaria citri. Moreover, they were found to be a slightly antifungal effective against Penicillium glabrum and Cladosporium cladosporioides. Anatomical studies were performed on leaf transverse and surface sections of L. aestivum and its bulb cross-section. The isobilateral leaf had tetracytic type of stomata. The mesophyll comprised arge lysigenous cavities and contained crystalline inclusions (raphide crystals). Large amounts of compound starch grains were recognized to occur in parenchyma cells in the bulb. SEM observations revealed that leaf epidermal cells had conspicuous boundaries and their membranes on periclinal walls were striate.

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Schiffrer, Eva Shannon, Matic Proj, Martina Gobec, Luka Rejc, Andrej Šterman, Janez Mravljak, Stanislav Gobec, and Izidor Sosič. "Synthesis and Biochemical Evaluation of Warhead-Decorated Psoralens as (Immuno)Proteasome Inhibitors." Molecules 26, no. 2 (January 12, 2021): 356. http://dx.doi.org/10.3390/molecules26020356.

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The immunoproteasome is a multicatalytic protease that is predominantly expressed in cells of hematopoietic origin. Its elevated expression has been associated with autoimmune diseases, various types of cancer, and inflammatory diseases. Selective inhibition of its catalytic activities is therefore a viable approach for the treatment of these diseases. However, the development of immunoproteasome-selective inhibitors with non-peptidic scaffolds remains a challenging task. We previously reported 7H-furo[3,2-g]chromen-7-one (psoralen)-based compounds with an oxathiazolone warhead as selective inhibitors of the chymotrypsin-like (β5i) subunit of immunoproteasome. Here, we describe the influence of the electrophilic warhead variations at position 3 of the psoralen core on the inhibitory potencies. Despite mapping the chemical space with different warheads, all compounds showed decreased inhibition of the β5i subunit of immunoproteasome in comparison to the parent oxathiazolone-based compound. Although suboptimal, these results provide crucial information about structure–activity relationships that will serve as guidance for the further design of (immuno)proteasome inhibitors.

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Ouaabou, Rachida, Said Ennahli, Bouchra Nabil, Lahcen Hssaini, Hafida Hanine, Francisca Hernández, Mourad Ouhammou, and Mostafa Mahrouz. "Multivariate Cherry Quality Assessment Using Morphological, Biochemical and Volatile Compound Traits." International Journal of Fruit Science 20, sup3 (July 2, 2020): S1328—S1347. http://dx.doi.org/10.1080/15538362.2020.1785988.

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Meldal, Morten. "‘One bead two compound libraries’ for detecting chemical and biochemical conversions." Current Opinion in Chemical Biology 8, no. 3 (June 2004): 238–44. http://dx.doi.org/10.1016/j.cbpa.2004.04.007.

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Malik, Parth, and Tapan K. Mukherjee. "Structure-Function Elucidation of Antioxidative and Prooxidative Activities of the Polyphenolic Compound Curcumin." Chinese Journal of Biology 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/396708.

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Phenolic compounds have been very well known for their antioxidant properties, owing to their unique ability to act as free radical scavengers which, in turn, is an outstanding attribute of their unique biochemical structure. Recent accumulating lines of evidence inculcate sustainable interest and curiosity towards the chemoprotective nature of the natural polyphenolic compound curcumin (diferuloylmethane) against oxidative stress-mediated disorders. Curcumin is naturally found as a constituent of dietary spices called turmeric, extracted from the plant Curcuma longa. However, like every phenolic antioxidant, curcumin possesses a concentration and medium dependent anti- and pro-oxidant behaviour. A detailed study of the structure-function analysis and the understanding of the mode of action of curcumin as well as its chemical analogues is thus essential to understand the selective biochemical consequences of curcumin. Moreover, the presence of transition metal ions, route of administration, and localized tissue are also the vital decisive factors to determine curcumin behaviour. With this viewpoint, this paper sheds lights on the medium dependent prooxidative and antioxidative attributes of curcumin. Further, with respect to emergence of nanocarriers, a brief discussion focusing on the biochemical effect exertion of curcumin chiefly due to targeted and slow release has also been added towards the end.

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Ocan, David, Zhang Rongrong, Martin Odoch, Ephraim Nuwamanya, Angele P. Ibanda, Thomas L. Odong, Jimmy Lamo, Anne M. Fitzgerald, Venea D. Daygon, and Patrick R. Rubaihayo. "Volatile Organic Compound Based Markers for the Aroma Trait of Rice Grain." Journal of Agricultural Science 12, no. 8 (July 15, 2020): 92. http://dx.doi.org/10.5539/jas.v12n8p92.

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A study was conducted to determine the volatile organic compounds (VOCs) associated with rice grain aroma in 37 commonly grown lines within Uganda, as well as elites. The aim of the study was to identify potential volatile biochemical markers, if any, for the rice grain aroma trait. Certified rice seeds were obtained from the Uganda National Crops Resources Research Institute germplasm collection. The seeds were sown into experimental plots, under field conditions and the mature paddy harvested. Polished rice grains were heated to 80 oC and the liberated VOCs subjected to untargeted metabolite analysis using gas chromatography-time-of-flight mass spectrometry. In total, nine functional groups were present; hydrocarbons, alcohols, ketones, aldehydes, N-containing compounds, S-containing compounds, esters, oxygen heterocycles and carboxylic acids. More specifically, 148 VOCs were identified across the 37 rice lines, of which 48 (32.4%) including 2-acetyl-1-pyrroline (2-AP) appeared to elucidate the difference between non-aromatic and aromatic rice. Furthermore, 41 (27.7%) VOCs were found to be significantly correlated with 2-AP abundance, the principle rice aroma compound. Amongst the 41 VOCs, only ten compounds were found to contribute highly towards variation in 2-AP abundance, indicative of their possible modulation roles in regard to rice aroma. Within the ten influential volatiles, three aroma active compounds; toluene, 1-hexanol, 2-ethyl and heptane, 2,2,4,6,6-pentamethyl- were established as the most reliable biochemical surrogates to the rice aroma trait. Thus, the aforementioned compounds may be used in rice breeding programme for enhancing development of the grain aroma trait.

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Bellis, Louisa J., Ruth Akhtar, Bissan Al-Lazikani, Francis Atkinson, A. Patricia Bento, Jon Chambers, Mark Davies, et al. "Collation and data-mining of literature bioactivity data for drug discovery." Biochemical Society Transactions 39, no. 5 (September 21, 2011): 1365–70. http://dx.doi.org/10.1042/bst0391365.

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The challenge of translating the huge amount of genomic and biochemical data into new drugs is a costly and challenging task. Historically, there has been comparatively little focus on linking the biochemical and chemical worlds. To address this need, we have developed ChEMBL, an online resource of small-molecule SAR (structure–activity relationship) data, which can be used to support chemical biology, lead discovery and target selection in drug discovery. The database contains the abstracted structures, properties and biological activities for over 700000 distinct compounds and in excess of more than 3 million bioactivity records abstracted from over 40000 publications. Additional public domain resources can be readily integrated into the same data model (e.g. PubChem BioAssay data). The compounds in ChEMBL are largely extracted from the primary medicinal chemistry literature, and are therefore usually ‘drug-like’ or ‘lead-like’ small molecules with full experimental context. The data cover a significant fraction of the discovery of modern drugs, and are useful in a wide range of drug design and discovery tasks. In addition to the compound data, ChEMBL also contains information for over 8000 protein, cell line and whole-organism ‘targets’, with over 4000 of those being proteins linked to their underlying genes. The database is searchable both chemically, using an interactive compound sketch tool, protein sequences, family hierarchies, SMILES strings, compound research codes and key words, and biologically, using a variety of gene identifiers, protein sequence similarity and protein families. The information retrieved can then be readily filtered and downloaded into various formats. ChEMBL can be accessed online at https://www.ebi.ac.uk/chembldb.

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Kwon, Jaeyoung, Keebeom Ko, Lijun Zhang, Dong Zhao, Hyun Ok Yang, and Hak Cheol Kwon. "An Autophagy Inducing Triterpene Saponin Derived from Aster koraiensis." Molecules 24, no. 24 (December 7, 2019): 4489. http://dx.doi.org/10.3390/molecules24244489.

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Autophagy is an important self-degradative mechanism that plays a key role in treating neurodegeneration diseases. This research aimed at discovering bioactive compounds from Aster koraiensis. A new triterpene saponin, astersaponin I (1), was isolated from the EtOH extract of A. koraiensis. The structure of 1 was characterized by spectroscopic methods, ECD calculation, and acid hydrolysis. The biochemical analysis showed that compound 1 significantly increased the expression of microtubule-associated protein 1A/1B light chain 3B (LC3-II) expression in SH-SY5Y cells, which indicates the induction of autophagy. Thus, further study may be needed to clarify whether compound 1 exerts beneficial effects on neurodegeneration diseases like Parkinson’s disease through autophagy induction.

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Grilli, Eleonora, Esterina Di Resta, Scognamiglio Monica, Severina Pacifico, Antonio Fiorentino, Thiago Assis Rodrigues Nogueira, Renata Concetta Vigliotti, and Antonio Ganga. "Soil phenolic compound variability in two Mediterranean olive groves." Plant, Soil and Environment 66, No. 5 (May 25, 2020): 207–15. http://dx.doi.org/10.17221/165/2020-pse.

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Phenolic compounds (PCs) – with special reference to secondary plant metabolites – were characterised in two Mediterranean olive groves (Olea europaea L.). Representative pedological profiles were dug to identify and characterise the pedotype. Qualitative and quantitative analyses were carried out on soil core samples gathered at fixed depths (0–20 cm and 20–40 cm) and olive leaf methanol extracts by high-performance liquid chromatography with ultraviolet detection. The total PCs content reflected the soil organic carbon distribution, especially carbon of humic and fulvic acids, corroborating their crucial role in humification pathways. Among the analysed plant secondary metabolites, luteolin-4'-O-glucoside and verbascoside were the most abundant in leaves and soils, respectively. Most of the easily hydrolysed/metabolised phenols were not found in soils. Rutin and verbascoside, despite containing glucose, strongly persisted in the soil environment, probably due to their allelopathic effect. Oleuropein was not found in soils because it is highly soluble and mobile in the soil environment. Furthermore, the presence of clay in soil seemed to determine the accumulation of specific PCs. Our data suggest that PCs persistence in soil seems to be mainly determined by a balance between physicochemical and biochemical instability and allelopathic stability rather than their abundance in the plant.

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Cui, Zhijuan, Bie Tan, Simeng Liao, Ming Qi, Xianze Wang, Andong Zha, Xiangfeng Kong, Yuguang Chen, Peng Liao, and José L. Campos. "Dietary Addition of Antioxidant Complex Packs and Functional Amino Acids Can Improve the Digestion, Absorption, and Immunity of Huanjiang Minipigs." BioMed Research International 2020 (September 29, 2020): 1–10. http://dx.doi.org/10.1155/2020/1475831.

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To study the effect of functional amino acids and the antioxidant function compound package on Huanjiang minipigs and to lay a foundation for the formulation of green and efficient feed for Huanjiang minipigs, we added functional amino acids and the antioxidant function compound package to piglet feed for 28 days. After feeding, we detected the growth performance, biochemical indexes, inflammatory indexes, and intestinal disaccharidase of piglets. It was found that functional amino acids and the antioxidant compound package had certain effects on the growth performance and biochemical indexes of piglets and could reduce the level of IL-6 and increase the level of LZM and SIgA of piglets, and the levels of lactase and maltase in the intestine also increased significantly. The results showed that the compound package of functional amino acids and antioxidation could improve the growth performance and immunity of piglets and promote the digestion and absorption of nutrients in piglets.

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MELLOR, Howard R., James NOLAN, Lea PICKERING, Mark R. WORMALD, Frances M. PLATT, Raymond A. DWEK, George W. J. FLEET, and Terry D. BUTTERS. "Preparation, biochemical characterization and biological properties of radiolabelled N-alkylated deoxynojirimycins." Biochemical Journal 366, no. 1 (August 15, 2002): 225–33. http://dx.doi.org/10.1042/bj20020466.

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We have reductively alkylated deoxynojirimycin imino sugars using sodium cyanoborohydride to provide an efficient means of generating a series of N-alkylated compounds containing 4–18 carbon side chains. The yields were greater than 90% using a variety of aldehydes of different chain lengths, and after purification were >95% pure using 1H-NMR. Radiolabelled compounds were prepared using sodium cyanoborotriti-ide to selectively label the first carbon atom in the alkyl chain and used in protein-binding and cell- and tissue-uptake experiments. Protein binding was chain-length-dependent with compounds of intermediate chain length (C9—C12), demonstrating an equal distribution between the aqueous and protein-bound phase. The extent of cell uptake also increased proportionally with increased chain length in a time-dependent manner. When administered to mice, the longer alkyl-chain compounds showed reduced absorption from the intestine and a marked deposition of compound in the liver and brain, suggesting that the more hydrophobic compounds were poorly cleared by the major tissues. In tissue-culture cells compounds with 8 or fewer carbon atoms were non-toxic and had CC50 (the concentration at which the number of cells or cell proliferation is reduced by 50%) values greater than 1mM. Compounds with chain lengths above C8 showed a chain-length-dependent increase in cytotoxicity. N-alkylated deoxynojirimycins (C4—C18) were evaluated for their inhibitory effects on ceramide-specific glucosyltransferase and glycoprotein-processing α-glucosidase. Increasing the alkyl chain length had little effect on α-glucosidase activity, but inhibition of ceramide-specific glucosyltransferase increased 10-fold when C4 and C9—C18 compounds were compared. Overall these data provide further definition of the molecular features of alkylated imino sugars that influence tissue selectivity and efficacy for cellular enzyme inhibition.

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Freiberg, C., J. Pohlmann, P. G. Nell, R. Endermann, J. Schuhmacher, B. Newton, M. Otteneder, T. Lampe, D. Häbich, and K. Ziegelbauer. "Novel Bacterial Acetyl Coenzyme A Carboxylase Inhibitors with Antibiotic Efficacy In Vivo." Antimicrobial Agents and Chemotherapy 50, no. 8 (August 2006): 2707–12. http://dx.doi.org/10.1128/aac.00012-06.

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ABSTRACT The pseudopeptide pyrrolidinedione antibiotics, such as moiramide B, have recently been discovered to target the multisubunit acetyl coenzyme A (acetyl-CoA) carboxylases of bacteria. In this paper, we describe synthetic variations of each moiety of the modularly composed pyrrolidinediones, providing insight into structure-activity relationships of biochemical target activity, in vitro potency, and in vivo efficacy. The novel derivatives showed highly improved activities against gram-positive bacteria compared to those of previously reported variants. The compounds exhibited a MIC90 value of 0.1 μg/ml against a broad spectrum of Staphylococcus aureus clinical isolates. No cross-resistance to antibiotics currently used in clinical practice was observed. Resistance mutations induced by pyrrolidinediones are exclusively located in the carboxyltransferase subunits of the bacterial acetyl-CoA carboxylase, indicating the identical mechanisms of action of all derivatives tested. Improvement of the physicochemical profile was achieved by salt formation, leading to aqueous solubilities of up to 5 g/liter. For the first time, the in vitro activity of this compound class was compared with its in vivo efficacy, demonstrating a path from compounds weakly active in vivo to agents with significant efficacy. In a murine model of S. aureus sepsis, the 100% effective dose of the best compound reported was 25 mg/kg of body weight, only fourfold higher than that of the comparator molecule linezolid. The obvious improvements achieved by chemical derivatization reflect the potential of this novel antibiotic compound class for future therapy.

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Todirascu Ciornea, Elena, Elena Grosu, Diana Elena Bucur, and Andrei Lobiuc. "Biochemical and Physiological Effects of Some Organic and Inorganic Chemical Agents in Capsicum spp." Revista de Chimie 69, no. 10 (November 15, 2018): 2703–7. http://dx.doi.org/10.37358/rc.18.10.6606.

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Cultivation of vegetables is expected to increase in order to meet the demands of the expanding populations of the globe. Meanwhile, anthropic activities increase the concentrations of various chemical compounds in aquatic and terrestrial habitats. For productivity and food safety reasons, assessments of effects of pesticides and metals on crops should be performed. In the current paper, the presence of some heavy metals and a pesticide compound in the substrate altered the levels of some Krebs cycle enzymes activities in pepper plants cultivated in controlled conditions. The photosynthetic apparatus of the same plants appeared relatively unaffected, while the potential/actual soil dehydrogenases ratios were increased in all treatments.

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Peters, Treutler, Döll, Kindt, Hankemeier, and Neumann. "Chemical Diversity and Classification of Secondary Metabolites in Nine Bryophyte Species." Metabolites 9, no. 10 (October 11, 2019): 222. http://dx.doi.org/10.3390/metabo9100222.

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The central aim in ecometabolomics and chemical ecology is to pinpoint chemical features that explain molecular functioning. The greatest challenge is the identification of compounds due to the lack of constitutive reference spectra, the large number of completely unknown compounds, and bioinformatic methods to analyze the big data. In this study we present an interdisciplinary methodological framework that extends ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) with data-dependent acquisition (DDA-MS) and the automated in silico classification of fragment peaks into compound classes. We synthesize findings from a prior study that explored the influence of seasonal variations on the chemodiversity of secondary metabolites in nine bryophyte species. Here we reuse and extend the representative dataset with DDA-MS data. Hierarchical clustering, heatmaps, dbRDA, and ANOVA with post-hoc Tukey HSD were used to determine relationships of the study factors species, seasons, and ecological characteristics. The tested bryophytes showed species-specific metabolic responses to seasonal variations (50% vs. 5% of explained variation). Marchantia polymorpha, Plagiomnium undulatum, and Polytrichum strictum were biochemically most diverse and unique. Flavonoids and sesquiterpenoids were upregulated in all bryophytes in the growing seasons. We identified ecological functioning of compound classes indicating light protection (flavonoids), biotic and pathogen interactions (sesquiterpenoids, flavonoids), low temperature and desiccation tolerance (glycosides, sesquiterpenoids, anthocyanins, lactones), and moss growth supporting anatomic structures (few methoxyphenols and cinnamic acids as part of proto-lignin constituents). The reusable bioinformatic framework of this study can differentiate species based on automated compound classification. Our study allows detailed insights into the ecological roles of biochemical constituents of bryophytes with regard to seasonal variations. We demonstrate that compound classification can be improved with adding constitutive reference spectra to existing spectral libraries. We also show that generalization on compound classes improves our understanding of molecular ecological functioning and can be used to generate new research hypotheses.

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Zheng, Yi-Chao, Long-Zhen Wang, Li-Jie Zhao, Li-Juan Zhao, Qian-Na Zhan, Jin-Lian Ma, Bin Zhang, et al. "1,2,3-Triazole-Dithiocarbamate Hybrids, a Group of Novel Cell Active SIRT1 Inhibitors." Cellular Physiology and Biochemistry 38, no. 1 (2016): 185–93. http://dx.doi.org/10.1159/000438620.

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Background/Aims: Human SIRT1 is reported to be involved in tumorgenesis, mainly due to its modulating effect on p53 by deacetylation on lysine382. A large quantity of SIRT1 inhibitors was applied in chemotherapeutic study, but few of them were applied into clinical trials. Methods and Results: In the current study, a novel series of compounds with 1,4-bispiperazinecarbodithioic acid methyl esters scaffold were characterized to have inhibitory potency to SIRT1 by molecular docking and biochemical evaluation. Further cell level study revealed that one of the most potent SIRT1 inhibitors, compound 3a, is cell active. It can upregulate the amount of p53 by accumulating the K382 acetylation of p53, which lead to the stabilization of p53 in human gastric cancer cell line MGC-803 cells. Meanwhile, we also found compound 3a can inactivate SIRT2 in cells, which suggests the compound as a non-selective SIRT inhibitor. Conclusion: All these findings indicate that compound 3a is a potent, reversible and cell active SIRT1 inhibitor and deserves further investigation as an anticancer agent or a biological tool.

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Abbade, Leticia Caravita, and Massanori Takaki. "Biochemical and physiological changes of Tabebuia roseoalba (Ridl.) Sandwith (Bignoniaceae) seeds under storage." Journal of Seed Science 36, no. 1 (2014): 100–107. http://dx.doi.org/10.1590/s2317-15372014000100013.

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Tabebuia roseoalba (Ridl.) Sandwith is a Brazilian forest species, with great use in landscaping and reforestation, occurring mainly in the semi-deciduous forest. Seeds are small, lightweight, winged and wind-dispersed. The objective of this study was to verify the physiological quality and biochemical changes in T. roseoalba seeds during 24-month storage. The following were assessed: germination, emergence, seedling length and seedling dry weight, content of lipids, proteins and phenolic compounds, and enzyme activity. Loss of seed quality during storage was evidenced by reduced germination and emergence, shorter seedling length and lower seedling dry weight, decreased content of lipids and proteins, decreased peroxidase and catalase activity, and increased phenolic compound content and polyphenol oxidase activity. Seeds should be stored and used within six months after collection.

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Danilenko, Lyudmila M., Sophiya Ya Skachilova, Sergey V. Nadezhdin, Alena Timokhina, Olesya V. Shcheblykina, and Alla S. Kotelnikova. "Pharmacological screening of substances with cardioprotective effect in the group of 3-oxypyridine derivatives." Research Results in Pharmacology 4, no. 2 (August 21, 2018): 125–31. http://dx.doi.org/10.3897/rrpharmacology.4.28414.

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Introduction: The search for new compounds with antihypoxic and cardioprotective effects among 3-oxypyridine derivatives is promising. Research objectives: To study the anti-hypoxic and cardioprotective effects of 3-oxypyridine derivatives. Materials and methods: The search for compounds with an antihypoxic effect was carried out on blood leukocytes of rats in in vitro. To simulate hypoxia, Oil for Tissue Culture (SAGE) was used, 500 µl of which was applied into wells over a growth medium in order to block gas exchange. The cardioprotective effect of 3-oxypyridine derivatives was studied in the model of coronary-occlusive myocardial infarction (30 minutes of ischemia, 90 minutes of reperfusion). The level of troponin I (Tn I) was determined as a biochemical marker of myocardial damage. Results and discussion: In the in vitro experiments, when culting white blood cells, the lead compound in the group of 3-oxypyridine derivatives was identified under code LKhT 21–16, which increases the number of viable cells in the presence of hypoxia, surpassing the reference drugs. When confirming the chemical structure of the lead compound, LHT 21–16, a high sensitivity of the NMR spectroscopy method was revealed. In studying the cardioprotective activity in the model of coronary-occlusive myocardial infarction compound LHT 21–16 exerted a marked cardioprotective effect when reducing the size of the necrotic zone and the level of biochemical marker Tn I. Conclusions: 3-oxypiridine derivatives have antihypoxic and cardioprotective effects, which shows in a high number of surviving cells in the presence of hypoxia in the in vitro model, a reduced size of the necrotic zone and a reduced level of Tn I in the coronary-occlusive myocardial infarction.

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Todorović, M. R., U. B. Mioč, I. Holclajtner-Antunović, and D. Šegan. "Synthesis and Characterization of Ammonium Decavanadate (V)." Materials Science Forum 494 (September 2005): 351–56. http://dx.doi.org/10.4028/www.scientific.net/msf.494.351.

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It is known that various polyoxovanadates interact specifically with enzymes, which is the main way of their biochemical activity. Therefore we have synthesized ammonium decavanadate, (NH4)6V10O28·6H2O. The novel compound was characterized by elemental and thermal analysis, X-ray powder and single crystal diffraction and IR and Raman spectroscopy. Its conductive properties have been studied, too. The spectroscopic analysis has shown the presence of hydrogen bonds of different strengths. In order to improve the biochemical activity of this compound and having in mind the presence of strong hydrogen bonds, we essayed the synthesis of complex of polyoxovanadate with alanine. The obtained product was characterized by the mentioned methods.

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Khatoon, Amana, Shafiq Ur Rehman, Muhammad Mudasar Aslam, Muhammad Jamil, and Setsuko Komatsu. "Plant-Derived Smoke Affects Biochemical Mechanism on Plant Growth and Seed Germination." International Journal of Molecular Sciences 21, no. 20 (October 20, 2020): 7760. http://dx.doi.org/10.3390/ijms21207760.

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The role of plant-derived smoke, which is changed in mineral-nutrient status, in enhancing germination and post-germination was effectively established. The majority of plant species positively respond to plant-derived smoke in the enhancement of seed germination and plant growth. The stimulatory effect of plant-derived smoke on normally growing and stressed plants may help to reduce economic and human resources, which validates its candidature as a biostimulant. Plant-derived smoke potentially facilitates the early harvest and increases crop productivity. Karrikins and cyanohydrin are the active compound in plant-derived smoke. In this review, data from the latest research explaining the effect of plant-derived smoke on morphological, physiological, biochemical, and molecular responses of plants are presented. The pathway for reception and interaction of compounds of plant-derived smoke at the cellular and molecular level of plant is described and discussed.

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Cadow, Joris, Jannis Born, Matteo Manica, Ali Oskooei, and María Rodríguez Martínez. "PaccMann: a web service for interpretable anticancer compound sensitivity prediction." Nucleic Acids Research 48, W1 (May 13, 2020): W502—W508. http://dx.doi.org/10.1093/nar/gkaa327.

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Abstract The identification of new targeted and personalized therapies for cancer requires the fast and accurate assessment of the drug efficacy of potential compounds against a particular biomolecular sample. It has been suggested that the integration of complementary sources of information might strengthen the accuracy of a drug efficacy prediction model. Here, we present a web-based platform for the Prediction of AntiCancer Compound sensitivity with Multimodal Attention-based Neural Networks (PaccMann). PaccMann is trained on public transcriptomic cell line profiles, compound structure information and drug sensitivity screenings, and outperforms state-of-the-art methods on anticancer drug sensitivity prediction. On the open-access web service (https://ibm.biz/paccmann-aas), users can select a known drug compound or design their own compound structure in an interactive editor, perform in-silico drug testing and investigate compound efficacy on publicly available or user-provided transcriptomic profiles. PaccMann leverages methods for model interpretability and outputs confidence scores as well as attention heatmaps that highlight the genes and chemical sub-structures that were more important to make a prediction, hence facilitating the understanding of the model’s decision making and the involved biochemical processes. We hope to serve the community with a toolbox for fast and efficient validation in drug repositioning or lead compound identification regimes.

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Picache, Jaqueline A., Bailey S. Rose, Andrzej Balinski, Katrina L. Leaptrot, Stacy D. Sherrod, Jody C. May, and John A. McLean. "Collision cross section compendium to annotate and predict multi-omic compound identities." Chemical Science 10, no. 4 (2019): 983–93. http://dx.doi.org/10.1039/c8sc04396e.

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Xia, Jue Liang, Bai Nian Ren, Yi Fan Tan, Pin Hua Rao, Tong Zhou Liu, and Wen Qi Zhang. "Extraction of Organic Compound from Carboxymethyl Cellulose Wastewater." Advanced Materials Research 807-809 (September 2013): 1219–22. http://dx.doi.org/10.4028/www.scientific.net/amr.807-809.1219.

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Carboxy methyl cellulose (CMC) wastewater contains high salinity (>10%) and chemical oxygen demand (COD) which results from organic by-products during production. It is usually necessary that the wastewater is pretreated before biochemical methods are employed. In this paper, distillation method was used to pretreat CMC wastewater and a kind of organic acid (Ethoxyacetic acid) was extracted. Effect of solution pH on the purity of ethoxyacetic acid was studied.

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Shang, Luqing, Shumei Zhang, Xi Yang, Jixue Sun, Linfeng Li, Zhengjie Cui, Qiuhong He, Yu Guo, Yuna Sun, and Zheng Yin. "Biochemical Characterization of Recombinant Enterovirus 71 3C Protease with Fluorogenic Model Peptide Substrates and Development of a Biochemical Assay." Antimicrobial Agents and Chemotherapy 59, no. 4 (November 24, 2014): 1827–36. http://dx.doi.org/10.1128/aac.04698-14.

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ABSTRACTEnterovirus 71 (EV71), a primary pathogen of hand, foot, and mouth disease (HFMD), affects primarily infants and children. Currently, there are no effective drugs against HFMD. EV71 3C protease performs multiple tasks in the viral replication, which makes it an ideal antiviral target. We synthesized a small set of fluorogenic model peptides derived from cleavage sites of EV71 polyprotein and examined their efficiencies of cleavage by EV71 3C protease. The novel peptide P08 [(2-(N-methylamino)benzoyl) (NMA)-IEALFQGPPK(DNP)FR] was determined to be the most efficiently cleaved by EV71 3C protease, with a kinetic constantkcat/Kmof 11.8 ± 0.82 mM−1min−1. Compared with literature reports, P08 gave significant improvement in the signal/background ratio, which makes it an attractive substrate for assay development. A Molecular dynamics simulation study elaborated the interactions between substrate P08 and EV71 3C protease. Arg39, which is located at the bottom of the S2 pocket of EV71 3C protease, may participate in the proteolysis process of substrates. With an aim to evaluate EV71 3C protease inhibitors, a reliable and robust biochemical assay with aZ′ factor of 0.87 ± 0.05 was developed. A novel compound (compound 3) (50% inhibitory concentration [IC50] = 1.89 ± 0.25 μM) was discovered using this assay, which effectively suppressed the proliferation of EV 71 (strain Fuyang) in rhabdomyosarcoma (RD) cells with a highly selective index (50% effective concentration [EC50] = 4.54 ± 0.51 μM; 50% cytotoxic concentration [CC50] > 100 μM). This fast and efficient assay for lead discovery and optimization provides an ideal platform for anti-EV71 drug development targeting 3C protease.

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Byrd, Chelsea M., Tove' C. Bolken, Adnan M. Mjalli, Murty N. Arimilli, Robert C. Andrews, Robert Rothlein, Tariq Andrea, Mohan Rao, Katrina L. Owens, and Dennis E. Hruby. "New Class of Orthopoxvirus Antiviral Drugs That Block Viral Maturation." Journal of Virology 78, no. 22 (November 15, 2004): 12147–56. http://dx.doi.org/10.1128/jvi.78.22.12147-12156.2004.

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ABSTRACT By using a homology-based bioinformatics approach, a structural model of the vaccinia virus (VV) I7L proteinase was developed. A unique chemical library of ∼51,000 compounds was computationally queried to identify potential active site inhibitors. The resulting biased subset of compounds was assayed for both toxicity and the ability to inhibit the growth of VV in tissue culture cells. A family of chemotypically related compounds was found which exhibits selective activity against orthopoxviruses, inhibiting VV with 50% inhibitory concentrations of 3 to 12 μM. These compounds exhibited no significant cytotoxicity in the four cell lines tested and did not inhibit the growth of other organisms such as Saccharomyces cerevisiae, Pseudomonas aeruginosa, adenovirus, or encephalomyocarditis virus. Phenotypic analyses of virus-infected cells were conducted in the presence of active compounds to verify that the correct biochemical step (I7L-mediated core protein processing) was being inhibited. Electron microscopy of compound-treated VV-infected cells indicated a block in morphogenesis. Compound-resistant viruses were generated and resistance was mapped to the I7L open reading frame. Transient expression with the mutant I7L gene rescued the ability of wild-type virus to replicate in the presence of compound, indicating that this is the only gene necessary for resistance. This novel class of inhibitors has potential for development as an efficient antiviral drug against pathogenic orthopoxviruses, including smallpox.

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Journal articles on the topic 'Biochemical compound'

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