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Abstract：
Prenylated flavonoids are an important class of naturally occurring flavonoids with important biological activity, but their low abundance in nature limits their application in medicines. Here, we showed the hemisynthesis and the determination of various biological activities of seven prenylated flavonoids, named 7-13, with an emphasis on antimicrobial ones. Compounds 9, 11, and 12 showed inhibitory activity against human pathogenic fungi. Compounds 11, 12 (flavanones) and 13 (isoflavone) were the most active against clinical isolated Staphylococcus aureus MRSA, showing that structural requirements as prenylation at position C-6 or C-8 and OH at positions C-5, 7, and 4\' are key to the antibacterial activity. The combination of 11 or 12 with commercial antibiotics synergistically enhanced the antibacterial activity of vancomycin, ciprofloxacin, and methicillin in a factor of 10 to 100 times against drug-resistant bacteria. Compound 11 combined with ciprofloxacin was able to decrease the levels of ROS generated by ciprofloxacin. According to docking results of S enantiomer of 11 with ATP-binding cassette transporter showed the most favorable binding energy; however, more studies are needed to support this result.
摘要：
戊烯化黄酮是一类重要的天然黄酮类化合物,具有重要的生物活性,但是它们在自然界中的低丰度限制了它们在药物中的应用。这里,我们展示了七种异戊烯黄酮的半合成和各种生物活性的测定，命名为7-13，重点是抗菌药物。化合物9、11和12对人类病原真菌显示出抑制活性。化合物11、12(黄烷酮)和13(异黄酮)对临床分离的金黄色葡萄球菌MRSA的活性最强,表明结构要求如C-6或C-8的异戊烯化和C-5、7和4'的OH是抗菌活性的关键。11或12与商业抗生素的组合协同增强了万古霉素的抗菌活性，环丙沙星,和甲氧西林对耐药细菌的10到100倍。化合物11联合环丙沙星能够降低环丙沙星产生的ROS水平。根据11的S对映体与ATP结合盒转运蛋白的对接结果，显示出最有利的结合能；然而，需要更多的研究来支持这一结果。
