Academic literature on the topic 'BIOAVAILABILITY RADAR'

ABSTRACT Colorectal cancer (CRC) is a pervasive malignancy that stands as a prominent contributor to global cancer-related mortality. Among the numerous causative factors, the overexpression of human epidermal growth factor receptor 2 (HER2) is notably linked to CRC progression. Acronychia (A.) pedunculata has a longstanding history in folk medicine due to its multifaceted medicinal attributes. This study aimed to assess the potential of specific bioactive compounds derived from A. pedunculata for their inhibition of HER2 in CRC, utilizing in silico analysis. The compounds were systematically evaluated through a series of computational analyses. Drug-likeness assessment, pharmacokinetic evaluation, and toxicity analysis were conducted. Molecular docking studies were performed to investigate binding affinities with the HER2 target. Additionally, bioavailability radar analysis was employed to predict oral bioavailability, while molecular target prediction provided insights into potential protein interactions. All 12 compounds demonstrated favorable drug-likeness properties and adherence to Lipinski’s rule of five, indicative of the potential for good oral bioavailability. Four compounds were found to have no toxicological endpoints. Molecular docking revealed two compounds, namely caryophylla-4 (14), 8 (15)-dien-5alpha-ol and (-)-globulol, which showed promising binding affinities between several compounds and HER2. From this study, two leads were identified from A. pedunculata. Further experimental studies are required to validate the action of leads.

In silico studies, are increasing now-a-days, as through computer mechanics, screening of novel compounds based upon their physicochemical properties is important to reduce the cost of synthesizing novel medicinal compounds. In silico studies by network analysis and throughout screening helps to know and calculate biological activity of medicinal compounds. Novel 9- benzylpurine derivatives synthesized previously are used to study its structure and bioavailability radar, physicochemical properties, lipophilicity, solubility, pharmacokinetics, drug likeness and medicinal chemistry properties. These properties are calculated by use of Chem draw, open babel[16] and SwissADME software available freely. The novel 9-benzyl-6-(furan-2-yl) -2-(N,N dimethylamino)-9H-purine compound[17] shows good druglikeness properties to make it orally active.

e14072 Background: Romidepsin (R) is indicated for cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma. Hypomagnesemia (HM) is common in these patients and is also listed in the Full Prescribing Information (FPI) for R. Moreover, since cardiac arrhythmias are associated with HM, patients exposed to R may be at higher risk. This study assessed whether HM was causally related to R exposure and to what extent magnesium (M) supplementation was undertaken in those with HM. Methods: We searched a large, U.S. patient data repository to detect all patients (aged 20-94 years) exposed to R (10/2010-01/2017). For these patients, serum M, as well as M supplementation data, was collected. Baseline M was assessed at initial R exposure, and HM was defined as either, a decline in M to < 1.8 mg/dL after R exposure or, in those with baseline M < 1.8 mg/dL, a decline in M by ≥0.1 mg/dL after R exposure. For each patient with HM after R exposure, the validated Naranjo Adverse Drug Reaction Probability Scale (NADRPS) was used to determine the probability that HM was caused by R. Results: Of 51 R-exposed CTCL (or other lymphoma) patients, 25 (49.0%) had HM. Of these 25, NADRPS scores yielded: 1 doubtful, 16 possible, 8 probable and 0 definite. Additionally, 24 of 25 patients with HM had documentation for presence or absence of M supplementation: 9 (37.5%) had supplementation with M agents considered to be bioavailable, 12 (50%) received M agents considered to have low bioavailability, and 3 (12.5%) had no M supplementation. Conclusions: In this study population, 25 of 51 (49.0%) patients had HM after R exposure, which appears to nearly double the percentage of patients described in the FPI. Moreover, 8 of 25 (32%) patients with HM had causality attributed to R exposure. In addition, 15 of 24 (63%) patients with HM received M supplementation with agents considered to have low bioavailability or received no M supplementation. These findings support the need for ongoing monitoring of R-exposed patients with low M, as well as the importance of repleting M with agents considered to be adequately bioavailable. Also, given that HM appears to be more frequent in this study population compared to pre-marketing data in the FPI, further studies are warranted.

In the early phases of drug development, prediction of pharmacokinetic parameters including absorption, distribution, metabolism, and elimination (ADME), before synthesis may be helpful in the selection of candidates with less significant pharmacokinetic profiles. 5-O-methyl-11-O-acetylalkannin (MAA) is naphthoquinone isolated from the roots of Alkanna genus, Alkanna cappadocica. The aim of the present study is to predict the in silico ADME study of MAA using web tool called SwissADME. The 2D structure of the compound was drawn on Chemdraw Ultra version 8.0. The colored zone represents the optimal physicochemical region for oral bioavailability, according to the bioavailability radar, which takes into account the characteristics of flexibility, lipophilicity, saturation, size, polarity, and solubility. The pharmacokinetic properties were analyzed using the boiled egg model. The yolk-colored yellow component has a high chance of entering the brain, whereas the white portion has a high chance of being passively absorbed by the gastrointestinal tract. The study concluded that MAA did not violate the recommended ranges for Lipinski’s rule of five, rotational bond count, and Topological Polar Surface Area (TPSA). MAA also showed moderate lipophilicity and good water solubility. It did not act as a substrate for P-glycoprotein. MAA displayed a potential to inhibit CYP1A2, CYP2C19, CYP2C9 and CYP3A4. Besides that, MAA exhibited no action against CYP2D6. It exhibited a uniform and good bioavailability score of 0.55 (55%) with high gastrointestinal (GI) absorption capabilities. Additionally, the Synthetic Accessibility score of the MAA represented easy-step reactions of synthesis. MAA does not violate any of the five drug-likeness parameters including Lipinski, Muegge, Ghose, Veber, and Egan rules. As a result, MAA could be considered a promising molecule in drug discovery. Moreover, the molecular docking analysis showed the formation of a stable protein ligand complex between TNFα and the ligand molecule.