IN SILICO ADME ANALYSIS AND MOLECULAR DOCKING APPLIED TO FLAVONOIDS TO FIND DRUG LEAD COMPOUNDS TARGETING DRD4

Mildred Garcia; Vaeeshnavi Buwa

doi:10.22159/ijms.2022.v10i4.45114

Authors

Mildred Garcia Department of Biology, Mindanao State University – Iligan Institute of Technology, Iligan, Philippines,
Vaeeshnavi Buwa Department of Bioinformatics, BioNome, Bengaluru, Karnataka, India.

DOI:

https://doi.org/10.22159/ijms.2022.v10i4.45114

Keywords:

ADME, molecular docking, flavonoids, DRD4, dopamine receptors, Glabrone

Abstract

Objective: The aim of this present study is to find flavonoids that can be potential drug lead compounds targeting the human D(4) Dopamine receptor (DRD4). Thirty-nine flavonoids were collected from the literature survey, and 23 of them were predicted by SwissTargetPrediction to have bioactivity toward DRD4.

Methods: ADME properties were evaluated, and molecular docking was executed. Among the flavonoids studied, Isovitexin, Glabridin, and Glabrone have shown better binding energy than the native ligand, Nemonapride. However, ADME analysis has demonstrated that Isovitexin has low GI absorption and is in the grey zone of the BOILED-egg. Glabridin is a BBB permeant but is a P-gp substrate. Glabrone has high GI absorption, and a P-gp non-substrate but not a BBB permeant.

Results and Conclusion: The experimental investigations and clinical evaluations are recommended to examine the mechanisms of their actions and other pharmacological effects and to validate the results of this in silico study. The scaffolds of these compounds can also be optimized to improve the few lapses and have better attributes as CNS drug lead candidates.

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