Computational pharmacology and computational chemistry of 4-hydroxyisoleucine: Physicochemical, pharmacokinetic, and DFT-based approaches

Computational pharmacology and chemistry of drug-like properties along with pharmacokinetic studies have made it more amenable to decide or predict a potential drug candidate. 4-Hydroxyisoleucine is a pharmacologically active natural product with prominent antidiabetic properties. In this study, ADM...

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Bibliographic Details
Published in:Frontiers in chemistry 2023-04, Vol.11, p.1145974-1145974
Main Authors: Ahmad, Imad, Kuznetsov, Aleksey E, Pirzada, Abdul Saboor, Alsharif, Khalaf F, Daglia, Maria, Khan, Haroon
Format: Article
Language:English
Subjects:
4-hydroxyisoleucine
Chemistry
computational chemistry
DFT
drug likeness
pharmacokinetics
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Summary:Computational pharmacology and chemistry of drug-like properties along with pharmacokinetic studies have made it more amenable to decide or predict a potential drug candidate. 4-Hydroxyisoleucine is a pharmacologically active natural product with prominent antidiabetic properties. In this study, ADMETLab 2.0 was used to determine its important drug-related properties. 4-Hydroxyisoleucine is compliant with important drug-like physicochemical properties and pharma giants' drug-ability rules like Lipinski's, Pfizer, and GlaxoSmithKline (GSK) rules. Pharmacokinetically, it has been predicted to have satisfactory cell permeability. Blood-brain barrier permeation may add central nervous system (CNS) effects, while a very slight probability of being CYP2C9 substrate exists. None of the well-known toxicities were predicted , being congruent with wet lab results, except for a "very slight risk" for respiratory toxicity predicted. The molecule is non ecotoxic as analyzed with common indicators such as bioconcentration and LC for fathead minnow and . The toxicity parameters identified 4-hydroxyisoleucine as non-toxic to androgen receptors, PPAR-γ, mitochondrial membrane receptor, heat shock element, and p53. However, out of seven parameters, not even a single toxicophore was found. The density functional theory (DFT) study provided support to the findings obtained from drug-like property predictions. Hence, it is a very logical approach to proceed further with a detailed pharmacokinetics and drug development process for 4-hydroxyisoleucine.
ISSN:2296-2646
2296-2646
DOI:10.3389/fchem.2023.1145974