PDF(Pubmed)
Abstract：
Flavonoids have various pharmacological activities, such as antihypertensive, anticancer, and and antidiabetic effects. Several studies have shown that luteolin, quercetin, kaempferol, myricetin, naringenin, hesperetin, and epicatechin have antihypertensive effects, but the mechanism of action has yet to be discovered with certainty. This study aims to identify flavonoids from luteolin, quercetin, kaempferol, myricetin, naringenin, hesperetin, and epicatechin as renin inhibitors through in silico study; seven flavonoid compounds were docked with 2V0Z with renin inhibitor (Aliskiren) in humans (Homo sapiens 6 LU7) using AutoDock v4.2.6. SwissADME was used to evaluate the pharmacokinetic characteristics of these substances. Results molecular binding of luteolin, quercetin, kaempferol, myricetin, naringenin, hesperetin, and epicatechin, has potential as renin inhibitors with affinity energy values lower than those of aliskiren of -9.3; -9.3; -10.0; -9.2; -9.9; -9.3; and -9.7 kcal/mol. The interactions of these seven compounds have the same catalytic activity as aliskiren on two aspartic acid residues, Asp32 and Asp215. The analysis of pharmacokinetic profiles and the search for physical and chemical properties showed that the seven compounds violated three of the five Lipinski rules, while aliskiren violated one. Hesperitin, kaempferol, and naringenin had similarities with aliskiren on the amino-acid residues in the renin-binding pocket. However, based on pharmacokinetic analysis, the three compounds had an oral pharmacokinetic profile that could have been better than aliskiren.
摘要：
黄酮类化合物具有多种药理活性,如抗高血压药，抗癌，和抗糖尿病作用。一些研究表明木犀草素,槲皮素,山奈酚,杨梅素,柚皮苷,Hesperetin,表儿茶素有降压作用，但是作用机制尚未确定。本研究旨在鉴定木犀草素中的黄酮类化合物,槲皮素,山奈酚,杨梅素,柚皮苷,Hesperetin,通过计算机研究，表儿茶素作为肾素抑制剂；使用AutoDockv4.2.6，将7种类黄酮化合物与2V0Z和肾素抑制剂（阿利基伦）对接。SwissADME用于评估这些物质的药代动力学特征。结果木犀草素的分子结合，槲皮素,山奈酚,杨梅素,柚皮苷,Hesperetin,还有表儿茶素,具有作为肾素抑制剂的潜力，其亲和力能值低于阿利吉仑的-9.3;-9.3;-10.0;-9.2;-9.9;-9.3;和-9.7kcal/mol。这七个化合物的相互作用与阿利吉仑对两个天冬氨酸残基具有相同的催化活性，Asp32和Asp215。药动学谱的分析和理化性质的寻找表明,这7种化合物违反了利平斯基5条规则中的3条,而Aliskiren侵犯了一个.Hesperitin,山奈酚,柚皮素在肾素结合袋中的氨基酸残基上与阿利吉仑相似。然而,基于药代动力学分析，这三种化合物的口服药代动力学特征可能比阿利吉仑更好。
