Seelam Jyostna, Satuluri V S A Kumar, Gupta S P, Anwer Zaihra
Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut 250005, India.
Indian J Biochem Biophys. 2011 Jun;48(3):158-63.
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.
在强心药（抗充血性心力衰竭药物）中，最重要的一类是洋地黄强心苷，但由于这些化合物的治疗指数较低，人们已开始关注通过抑制Na +，K（+）-ATP酶来研究更安全的强心药，洋地黄强心苷正是通过该机制发挥作用。最近，人们对一系列全氢化茚进行了研究，以考察它们对Na +，K（+）-ATP酶的抑制活性。我们在此报告一项关于它们的定量构效关系（QSAR）研究，以探究决定其活性的分子的物理化学和结构性质，从而使结构修饰更合理，以获得更有效的药物。多元回归分析表明，这些化合物的Na +，K（+）-ATP酶抑制活性与其R5取代基的基尔一阶价分子连接性指数及一些指示参数之间存在显著相关性，这表明含有低价高饱和度原子的化合物的R5取代基以及具有=N - O -部分的R1取代基将有利于活性。
