title: A QSAR study on a series of simplified digitalis-like compounds acting on Na+,K(+)-ATPase.
abstract: Among the cardiotonics (agents against congestive heart failure), the most important group is of the digitalis cardiac glycosides, but since these compounds suffer from a low therapeutic index, attention has been paid to investigating safer cardiotonic agents through the inhibition of Na+,K(+)-ATPase, the mechanism by which the digitalis cardiac glycosides elicit their action. Recently, a series of perhydroindenes were studied for their Na+,K(+)-ATPase inhibition activity. We report here a QSAR study on them to investigate the physicochemical and structural properties of the molecules that govern their activity in order to rationalize the structural modification to have more potent drugs. A multiple regression analysis reveals a significant correlation between the Na+,K(+)-ATPase inhibition activity of the compounds and Kier's first order valence molecular connectivity index of their R5-substituents and some indicator parameters, suggesting that the R5-substituents of the compounds containing atoms with low valence and high saturation and the R1-substituents having =N-O- moiety will be conducive to the activity.
authors.affiliation: Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut 250005, India.
authors.forename: Jyostna
authors.initials: J
authors.lastname: Seelam
authors.forename: V S A Kumar
authors.initials: VS
authors.lastname: Satuluri
authors.forename: S P
authors.initials: SP
authors.lastname: Gupta
authors.forename: Zaihra
authors.initials: Z
authors.lastname: Anwer
mesh_terms: D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D004070:Digitalis / Q000737:chemistry*; D004071:Digitalis Glycosides / Q000037:antagonists & inhibitors / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
chemical_list: D002316:Cardiotonic Agents; D004071:Digitalis Glycosides; D004791:Enzyme Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase