Open AccessComputer-aided Validation of Fluorobenzimidazole as Soluble Epoxide Hydrolase Inhibitor: An In-Silico Study
Author(s) -
Bedanta Bhattacharjee,
Ritu Bharti,
Karabi Kalita,
Nirupam Das,
Abu Md Ashif Ikbal
Publication year - 2021
Publication title -
pharmaceutical and biosciences journal
Language(s) - English
Resource type - Journals
ISSN - 2582-0540
DOI - 10.20510/pbj/9/i2/1487
Subject(s) - epoxide hydrolase 2 , lipinski's rule of five , in silico , docking (animal) , chemistry , protein data bank (rcsb pdb) , active site , stereochemistry , epoxide hydrolase , benzoic acid , enzyme , biochemistry , gene , medicine , nursing , microsome
Soluble epoxide hydrolase (sEH) is an enzyme and is encoded by the gene EPHX2 in human beings. Indeed, by inhibiting the biotransformation of these epoxide(s) via arresting the action of the mammalian sEH one can develop a promising antihypertensive drug(s). The present work was emphasized the possible binding mode of fifteen fluorobenzimidazole (4a-4o) derivatives as soluble epoxide hydrolase (sEH) inhibitors. The X-ray crystal structure of human sEH in complex with the inhibitor 6NJ [(3-(2-phenylethyl)-1H-indazole] has been utilized to select the specific active site of protein data bank (PDB) ID: 5AKY with resolution: 2.18 Å for the docking study.The energy conformer of trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB) was docked using the prepared grid towards validation of the generated grid and docking protocol. The best results obtained by the ligands 4f, 4g and 4m with a dock score -9.94, -9.75, and -11.56, respectively. Among all the ligands, 4m exhibited considerable “drug-like” characteristics with the highest G score and possess acceptable in-silico pharmacokinetic by obeying Lipinski rule of five. In conclusion, compound 4m might be used as a lead molecule in the antihypertensive drug discovery.