title: Ab initio study of non-peptidic antihypertensives.
abstract: In this study, the authors report ab initio molecular orbital calculations on natural hormone angiotensin II (ANG II) that induces activity at AT(1) receptor leading to vasoconstriction and subsequent hypertension. Optimized conformations and charge distributions of various conformers of natural hormone and AT(1) antagonists have been studied. The major pharmacophoric features have been deduced. The charge environment of ANG II and drugs guided us in exploring the two possibilities: substrate inhibition and competitive inhibition. The results indicate that more potent drugs avoid 'wastage' in substrate inhibition and undergo strong competitive antagonism at the receptor. Specific binding interactions are essential for competitive antagonism. Slight differences in conformation may effect to differences in interactions with the receptor, hence modulating the antagonistic properties of the drug.
authors.affiliation: Department of Chemistry, University Institute of Engineering and Technology, C.S.J.M. University, Kanpur - 208024, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Jain
authors.forename: Arpita
authors.initials: A
authors.lastname: Yadav
mesh_terms: D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology*; D019295:Computational Biology; D003198:Computer Simulation; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000959:Antihypertensive Agents; D010455:Peptides; D000804:Angiotensin II; D000803:Angiotensin I