Relevant bibliographies by topics / Beta lactam antibiotics – Synthesis

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Academic literature on the topic 'Beta lactam antibiotics – Synthesis'

Author: Grafiati
Published: 4 June 2021
Last updated: 13 February 2022

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Journal articles on the topic "Beta lactam antibiotics – Synthesis"

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Vondracek, Thomas G. "Beta-Lactam Antibiotics: Is Continuous Infusion The Preferred Method of Administration?" Annals of Pharmacotherapy 29, no. 4 (April 1995): 415–24. http://dx.doi.org/10.1177/106002809502900413.

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Objective: To examine the pharmacodynamic properties of the beta-lactam class of antibiotics and the rationale for their continuous infusion (CI), and to explore reasons that this mode of administration has not replaced intermittent infusion as the standard of practice. Data Sources: A MEDLINE search of the English-language literature evaluating CI administration of beta-lactam antibiotics was conducted. Bibliographic searches of these articles also were performed. Study Selection: Because there were few human trials, all available trials were considered for review. A cross section of clinical trials, animal studies, and in vitro studies examining the impact of the route of antibiotic administration was selected for each pharmacodynamic variable addressed. Data Synthesis: The support for CI as the preferred method of beta-lactam administration comes primarily from in vitro and animal data. Most beta-lactam antibiotics do not demonstrate concentration-dependent killing and have an appreciable postantibiotic effect only against gram-positive cocci. Their efficacy appears to be optimized by maintaining suprainhibitory concentrations throughout the dosing interval. Therefore, CI of beta-lactams could potentially enhance the efficacy of treatment or allow less drug to be used on a daily basis. This has yet to be demonstrated convincingly in human clinical trials. Comparative trials need to continue to explore die impact of the method of administration on patient outcomes such as duration and cost of therapy, as well as morbidity and mortality. Conclusions: Results of many animal and in vitro studies suggest that CI may be the optimal method of beta-lactam administration. Clinical trials need to further document the impact of the method of beta-lactam administration on the incidence of adverse effects, emergence of bacterial resistance, and patient outcome. Pharmacodynamic studies defining target beta-lactam concentrations, the practicality of CI in patients requiring multiple intravenous fluids and medications, and the pertinence of this issue when beta-lactam antibiotics are used as sole agents or in combination with other antimicrobials require further exploration.
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Filippova, A. A., M. Yu Rubtsova, M. M. Ulyashova, and N. K. Fursova. "Expression of beta-lactamase genes in multidrug-resistant bacteria." Bacteriology 5, no. 3 (2020): 34–46. http://dx.doi.org/10.20953/2500-1027-2020-3-34-46.

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Antimicrobial resistance is a global public health problem. In recent years, increasing of multi-drug resistant bacteria has been noted, which are resistant to different antimicrobial groups simultaneously, including beta-lactams. The main mechanism of anti-beta-lactam resistance in gram-negative bacteria is synthesis of various beta-lactamases that hydrolyze the antibiotics. The review is devoted to the analysis of data on the expression of beta-lactamase genes by multi-drug resistant bacteria and molecular genetic methods for their determination in RNA transcripts. Key words: antibiotic resistance, transcriptome, molecular genetic methods, beta-lactamases
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Mandel, Martin, Ludvík Novák, Miroslav Rajšner, Jiří Holubek, and Vladislava Holá. "New synthesis of oxime-type beta-lactam antibiotics." Collection of Czechoslovak Chemical Communications 54, no. 6 (1989): 1734–45. http://dx.doi.org/10.1135/cccc19891734.

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Reaction of anhydrous acids II with phosphorus pentachloride afforded hydrochlorides of chlorides III which were used in acylations of N,O-bis(trimethylsilyl) derivatives of 6-aminopenicillanic and 7-aminodeacetoxycephalosporanic acid. Change of the (Z)-configuration of the alkoxyimino group during the synthesis was observed only in the methoxyimino series. The prepared penicillins IV are effective against gram-positive as well as gram-negative bacteria.
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Salamone, Francine R. "Sulbactam/Ampicillin." Infection Control & Hospital Epidemiology 9, no. 7 (July 1988): 323–27. http://dx.doi.org/10.1086/645863.

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Sulbactam/ampicillin was recently marketed for use in several infections caused by beta-lactamase-producing organisms. Sulbactam is the second beta-lactamase inhibitor to become available in the United States. Interest in inhibition of beta-lactamases arose in the late 1960s when a combination consisting of an antibacterial agent and an enzyme inhibitor was found effective in the treatment of certain resistant gram-negative infections. It is now well accepted that the addition of a beta-lactamase inhibitor to a beta-lactam antibiotic may expand its usefulness in a variety of infections.The penicillin derivatives, known as beta-lactam antibiotics, possess a four-membered ring (beta-lactam ring) fused to a second ring (Figure). It is the beta-lactam ring that is essential for the inhibition of bacterial cell wall synthesis and subsequent bactericidal activity of these agents. The development of resistance to beta-lactam antibiotics may occur by a number of mechanisms, although the most important is bacterial production of enzymes (beta-lactamases) that are capable of beta-lactam ring hydrolysis and inactivation.Sulbactam resembles the penicillin derivatives in structure (Figure) and is able to preserve their activity by its ability to inhibit the action of beta-lactamases, particularly those of the Richmond classes II-V (gram-negative) and the group A beta-lactamases (gram-positive). Sulbactam is referred to as a “suicide inhibitor” because while forming an irreversible complex with the enzyme, it is destroyed in the process. By virtue of its ability to render the beta-lactamases inactive, sulbactam has been combined with ampicillin in an effort to restore its activity against a number of pathogens that have developed resistance by this mechanism.
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SKOTNICKI, JERAULD S., and BRUCE A. STEINBAUGH. "Synthesis and antibacterial activity of novel aminothiazolyl .BETA.-lactam derivatives." Journal of Antibiotics 39, no. 3 (1986): 372–79. http://dx.doi.org/10.7164/antibiotics.39.372.

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Miller, Marvin J. "Hydroxamate approach to the synthesis of .beta.-lactam antibiotics." Accounts of Chemical Research 19, no. 2 (February 1986): 49–56. http://dx.doi.org/10.1021/ar00122a004.

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ASZODI, J. "Design and synthesis of bridged $gamma;-lactams as analogues of $beta;-lactam antibiotics." Bioorganic & Medicinal Chemistry Letters 14, no. 10 (May 2004): 2489–92. http://dx.doi.org/10.1016/s0960-894x(04)00332-4.

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Burroughs, SF, and GJ Johnson. "Beta-lactam antibiotic-induced platelet dysfunction: evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin." Blood 75, no. 7 (April 1, 1990): 1473–80. http://dx.doi.org/10.1182/blood.v75.7.1473.1473.

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Abstract beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of [14C]-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; but no irreversible inhibition of alpha 2 adrenergic receptors, measured with [3H]-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist [3H]-U46619 and antagonist [3H]-SQ29548, occurred. However, low- affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ([Ca2+]i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in [Ca2+]i. The loss of low- affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane.
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Burroughs, SF, and GJ Johnson. "Beta-lactam antibiotic-induced platelet dysfunction: evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin." Blood 75, no. 7 (April 1, 1990): 1473–80. http://dx.doi.org/10.1182/blood.v75.7.1473.bloodjournal7571473.

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beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of [14C]-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; but no irreversible inhibition of alpha 2 adrenergic receptors, measured with [3H]-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist [3H]-U46619 and antagonist [3H]-SQ29548, occurred. However, low- affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ([Ca2+]i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in [Ca2+]i. The loss of low- affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane.
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KAWABATA, KOHJI, TAKASHI MASUGI, and TAKAO TAKAYA. "Studies on .BETA.-lactam antibiotics. XII. Synthesis and activity of new 3-ethynylcephalosporin." Journal of Antibiotics 39, no. 3 (1986): 394–403. http://dx.doi.org/10.7164/antibiotics.39.394.

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Dissertations / Theses on the topic "Beta lactam antibiotics – Synthesis"

1

Hadfield, Peter Stanley. "The synthesis of #gamma#-lactam mimics of #beta#-lactam antibiotics." Thesis, University of Huddersfield, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338614.

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Schofield, C. "Chemical and enzymatic synthesis of beta-lactam antibiotics." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355775.

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Freeman, Richard Neil Templar. "The total synthesis of non-beta-lactam antibiotics." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.257963.

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Knight, J. "New synthetic methods for the synthesis of #BETA#-lactam antibiotics." Thesis, University of Southampton, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373921.

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Cox, G. "Synthesis of carbocyclic analogues of the #beta#-lactam antibiotics." Thesis, University of Huddersfield, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374894.

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Sakhnini, Nina Issam. "The synthesis of novel compounds related to #beta#-lactam antibiotics." Thesis, University of Sussex, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359204.

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Goh, Kee Chuan. "The biosynthesis of β-lactams." Thesis, University of Oxford, 1993. http://ora.ox.ac.uk/objects/uuid:24b6b29d-87cc-48f2-bd1b-bb64c663604f.

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This thesis reports the work done on two research projects which were carried out independently of each other but converge on the central theme of β-lactam biosynthesis. Chapter 1 provides an overview of biosynthesis in secondary metabolism, with special emphasis on current knowledge about the β-lactams. The first project, covered from Chapters 2 to 5, was part of our group's continuing effort to understand the structure and mechanism of Ring Expandase-Hydroxylase (REXH), an enzyme involved in the biosynthesis of cephalosporin C in Cephalosporium acremonium. REXH is a bifunctional enzyme, converting penicillin N to DAOC and thence to DAC. [diagram omitted from transcription] Chapter 3 discusses the investigation of purification protocols for native REXH and soluble recombinant REXH, as well as an improved refolding method for recombinant REXH expressed as inclusion bodies. Chapter 4 describes two new alternative substrates for REXH, viz. carba-DAOC and DAC, whilst the y-lactam analogue of penicillin N was not found to be a substrate for REXH. Chapter 5 summarises some structural investigations of REXH employing methods such as electrospray mass spectrometry, selective proteolysis and inhibition kinetics. [diagram omitted from transcription] The second project, covered from Chapters 6 to 9, represents the first biosynthetic studies on valclavam, an antifungal produced by Streptomyces antibioticus. Valclavam belongs to the family of clavams which includes clavulanic acid as its most well studied member. [diagram omitted from transcription] Chapter 7 details the development of methods for the bioassay, fermentation and isolation of valclavam. It also describes the isolation of a stable degradation fragment of valclavam which led to the revision of the structures of valclavam and Tü 1718B (another metabolite from the same organism). Chapter 8 gives an account of the whole-cell feeding experiments which strongly suggest that the primary metabolic precursors for valclavam are L-valine, L-arginine, L-methionine and glycerol. Chapter 9 reports the discovery of two enzymic activities, belonging to those of clavaminic acid synthase and proclavaminic acid amidino hydrolase, which are likely to be involved in the biosynthesis of valclavam. Together, the results of Chapters 8 and 9 point to an extensive overlap between the clavulanic acid pathway in Streptomyces clavuligerus and the valclavam pathway in Streptomyces antibioticus.
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Sayer, P. "The synthesis of #beta#-lactam antibiotic analogues." Thesis, Lancaster University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235587.

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Templey, Margaret Patricia. "The synthesis of some new heterocyclic analogues of the beta-lactam antibiotics." Thesis, University of Bath, 1988. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384557.

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Khan, Tariq Hussain. "Approaches to the synthesis of β-lactam antibiotics." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/12361.

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Books on the topic "Beta lactam antibiotics – Synthesis"

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Alcaide, B., and Bimal K. Banik. Heterocyclic scaffolds I: Ss-lactams. Heidelberg: Springer, 2010.

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Bruggink, Alle, ed. Synthesis of β-Lactam Antibiotics. Dordrecht: Springer Netherlands, 2001. http://dx.doi.org/10.1007/978-94-010-0850-1.

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Bolister, Nina Jane. The diffusion of beta-lactam antibiotics through biopolymers. Brighton: Brighton Polytechnic Department ofPharmacy, 1989.

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Washington, John A. The role of beta-lactamases in microbial resistance to beta-lactam antibiotics. Kalamazoo, Mich: Upjohn, 1986.

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Kawamoto, Isao. Antibiotics I: [beta]-lactams and other antimicrobial agents. Switzerland: Gordon and Breach Science Publishers, 1992.

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Molekulare Analysen zur Expression von gbs-Lactam-Genen bei Acremonium chrysogenum. Berlin: J. Cramer, 1992.

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Bellido, F. The new -lactams: Mode of action, mechanisms of resistance. Basle, Switzerland: Roche, 1989.

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Gangwer, Michael I. On-farm screening tests for beta-lactam residues in milk. [Corvallis, Or.]: Oregon State University Extension Service, 1994.

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Gangwer, Michael I. On-farm screening tests for beta-lactam residues in milk. [Corvallis, Or.]: Oregon State University Extension Service, 1994.

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Gangwer, Michael I. On-farm screening tests for beta-lactam residues in milk. [Corvallis, Or.]: Oregon State University Extension Service, 1994.

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Book chapters on the topic "Beta lactam antibiotics – Synthesis"

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Neuhauser, Melinda M., and Larry H. Danziger. "Beta-Lactam Antibiotics." In Drug Interactions in Infectious Diseases, 151–84. Totowa, NJ: Humana Press, 2001. http://dx.doi.org/10.1007/978-1-59259-025-4_7.

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Cojocel, Constantin. "Beta-lactam antibiotics." In Clinical Nephrotoxins, 171–98. Dordrecht: Springer Netherlands, 2003. http://dx.doi.org/10.1007/1-4020-2586-6_9.

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Page, Malcolm G. P. "Beta-Lactam Antibiotics." In Antibiotic Discovery and Development, 79–117. Boston, MA: Springer US, 2011. http://dx.doi.org/10.1007/978-1-4614-1400-1_3.

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Bhandari, Prasan. "Beta-lactam antibiotics." In Pharmacology Mind Maps for Medical Students and Allied Health Professionals, 513–24. Boca Raton, FL : CRC Press/Taylor & Francis, 2020.: CRC Press, 2019. http://dx.doi.org/10.1201/9780429023859-57.

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Cojocel, Constantin. "Beta-lactam antibiotics." In Clinical Nephrotoxins, 293–321. Boston, MA: Springer US, 2008. http://dx.doi.org/10.1007/978-0-387-84843-3_13.

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Danziger, Larry H., and Melinda Neuhauser. "Beta-Lactam Antibiotics." In Drug Interactions in Infectious Diseases, 203–42. Totowa, NJ: Humana Press, 2011. http://dx.doi.org/10.1007/978-1-61779-213-7_7.

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Danziger, Larry H., and Karolyn S. Horn. "Beta-Lactam Antibiotics." In Drug Interactions in Infectious Diseases: Antimicrobial Drug Interactions, 1–56. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-72416-4_1.

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Barredo, José-Luis, Gulay Ozcengiz, and Arnold L. Demain. "Advances in Beta-Lactam Antibiotics." In Antimicrobial Compounds, 115–47. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-40444-3_5.

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Muller, Anouk E., and Johan W. Mouton. "Continuous Infusion of Beta-lactam Antibiotics." In Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics, 223–55. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-0-387-75613-4_10.

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Bruggink, Alle, and Peter D. Roy. "Industrial Synthesis of Semisynthetic Antibiotics." In Synthesis of β-Lactam Antibiotics, 12–54. Dordrecht: Springer Netherlands, 2001. http://dx.doi.org/10.1007/978-94-010-0850-1_1.

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Conference papers on the topic "Beta lactam antibiotics – Synthesis"

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Luo, Qijian, and Yiqi JIn. "Oral Beta-lactamase Protects the Gut Bifidobacterium/Lactobacillus from Beta-lactam Antibiotics-mediated Damage in SD Rats." In ICBBS '20: 2020 9th International Conference on Bioinformatics and Biomedical Science. New York, NY, USA: ACM, 2020. http://dx.doi.org/10.1145/3431943.3431948.

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Núñez-Núñez, M., R. Morón-Romero, R. Álvarez-Sánchez, J. García Villanova, N. Chueca, S. Portillo-Haro, E. Yuste-Ossorio, and J. Cabeza-Barrera. "4CPS-048 Beta-lactam antibiotics in critical ill patients: are we dosing our patients correctly?" In 25th EAHP Congress, 25th–27th March 2020, Gothenburg, Sweden. British Medical Journal Publishing Group, 2020. http://dx.doi.org/10.1136/ejhpharm-2020-eahpconf.149.

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Pareek, Chandresh. "An Efficient Combinatorial Approach for Beta-Lactam Antibiotics with Novel Adjuvants against Gram-Negative Organisms to Combat Multi-Drug Resistance." In International conference on Applied Research in Engineering, Science and Technology. ACAVENT, 2018. http://dx.doi.org/10.33422/icarest.2018.09.47.

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Torgunakova, Ekaterina Sergeevna, Elena Nikolaevna Bochanova, Irina Vladimirovna Demko, Angelina Yur'Evna Kraposhina, and Evgeniya Mikhailovna Kurts. "Active monitoring of adverse drug reactions to the use of beta-lactam antibiotics in the treatment of community-acquired pneumonia." In ERS International Congress 2020 abstracts. European Respiratory Society, 2020. http://dx.doi.org/10.1183/13993003.congress-2020.1781.

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"Molecular composition - inhibition activity relationships for humic substances narrow fractions sets obtained by solid-phase extraction." In Sixth International Conference on Humic Innovative Technologies "Humic Substances and Eco-Adaptive Technologies ”(HIT – 2021). Non-Commercial Partnership "Center for Biogenic Resources "Humus Sapiens" (NP CBR "Humus Sapiens"), 2021. http://dx.doi.org/10.36291/hit.2021.mikhnevich.001.

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Humic substances (HS) have a wide spectrum of biological activity including inhibitory activity against β-lactamases.1 The latter are capable of hydrolyzing beta-lactam antibiotics and represent one of the main pathways of bacterial antibiotic resistance. HS are characterized by low toxicity and good solubility in water. A use of HS for therapeutic purposes is hindered by extreme molecular heterogeneity and high level of isomeric complexity. Solid-phase extraction (SPE) fractionation in combination with ultra-high resolution mass spectrometry (FTICR MS) is a promising method to simplify this molecular system and isolate the most active components of HS. The aim of this work was to test various SPE fractionation schemes as an approach to directed isolation of the components with the given activity from HS. The sample of coal humic acids (CHA-G) was isolated from the commercial sodium humate “Genesis” and separated using SPE cartridge according to gradients in polarity1 and acidity2 inherent within the molecular components of HS. Inhibitory activity against β- lactamase TEM-1 and its mutants was measured using chromogenic substrate CENTA. Molecular composition of fractions was determined using FTICR mass spectrometer 15 T solariX (Bruker Daltonics) located at the Collective Use Center of Zelinsky Institute of Organic Chemistry of RAS. Molecular assignments were plotted into van Krevelen diagrams. The diagrams were binned into 20 cells are assigned to seven chemotypes, and occupational densities for each chemotype were calculated after Perminova.3 For the fractions separated by polarity, a substantial difference in the molecular composition was observed. Inhibitory activity grew along with an increase in hydrophobicity. The HS activity increased along with an increase in contribution of condensed tannins and phenylisopropanoids (O/C <0.5, H/C <1.4) and decreased along with contribution of hydrolyzed tannins (O/C> 0.5, H/C <1.4). The similar analysis was conducted for the fractions separated with regard to pKa value of the dominating functional groups. The most isomeric complex molecular components were defined, which can be found in different HS fractions, but they are identical in elemental composition. The data obtained make it possible to choose the most efficient fractionation method that effectively lowers the molecular complexity of HS and makes it possible to isolate the most active HS fractions. SPE-fractionation in combination with 2D chromatography is going to be used in our future studies to achieve high resolution separation and more reliable “molecular composition-activity” relationships. Further research might bring substantial advance in the field of directed design of biologically active humic-based materials and compositions. Acknowledgements. This work was supported by the grant of the Russian Science Foundation no 21-73-20202. The center of collective use of the Zelinsky IOC RAS is appreciated. The research was conducted in the framework of the Scientific-Educational School of the Lomonosov MSU “Future of the plant and global environmental change”. References 1. Mikhnevich et al., ACS Omega, 2021, https://doi.org/10.1021/acsomega.1c02841 2. Zherebker et al., Environ. Sci. Technol. 2020, 54, 2667−2677 3. Perminova, I. V. PAC, 2019, 91(5), 851
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Reports on the topic "Beta lactam antibiotics – Synthesis"

1

Dou, Q. P. Synthetic Beta-Lactam Antibiotics as a Selective Breast Cancer Cell Apoptosis Inducer: Significance in Breast Cancer Prevention and Treatment. Fort Belvoir, VA: Defense Technical Information Center, March 2007. http://dx.doi.org/10.21236/ada572620.

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