类黄酮化合物抑制NDM-1活性的构效关系

Structure-activity Relationship between Structure of Flavonoids and Inhibition of NDM-1

选择食物来源相对丰富且分子结构具有一定差异的3种类黄酮化合物(槲皮素、木犀草素、染料木黄酮),通过碘量法比较它们对新德里金属β内酰胺酶-1(NDM-1)的抑制活性。通过分子对接软件分析化合物对NDM-1的理论结合能力,建立类黄酮化合物抑制NDM-1活性的构效关系。碘量法分析结果表明,3种类黄酮化合物对NDM-1抑制活性差异表现为染料木黄酮>木犀草素>槲皮素,这一结果与分子对接理论分析结果一致。由此,3种化合物抑制NDM-1的构效关系为:B环处于C环3位(染料木黄酮),是抑制NDM-1的相对优势结构;而C环3位羟基(槲皮素)对抑制NDM-1活性具有一定削弱作用。

In this study, three flavonoids（quercetin, luteolin, genistein） with different structure, which are abundant in plant food, were selected to compare their inhibitory activities to New Delhi metal β-lactamase-1（NDM-1） by iodimetry, analyze theoretically the binding capacity of flavonoids to NDM-1 by molecular docking software, and establish the structure-activity relationship between structure of flavonoids and inhibition of NDM-1. Iodimetry analysis showed that the inhibitory effect of three flavonoids on NDM-1 was as follows： genistein〉 luteolin 〉quercetin. This result was consistent with theoretical analysis of molecular docking. Thus, the structure-activity relationship between three flavonoids and inhibition of NDM-1 was shown that： genistein with 3-B ring was the relative advantage structure, but quercetin with the 3-hydroxy showed a weakening effect on inhibition of NDM-1.