Laboratory of Natural Medicine and Microbiological Drug, College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang, 330045, China.
Biotechnological Engineering Center for Pharmaceutical Research and Development, Jiangxi Agricultural University, Nanchang, 330045, China.
Sci Rep. 2021 May 18;11(1):10471. doi: 10.1038/s41598-021-90035-7.
Antimicrobial resistance seriously threatened human health, and new antimicrobial agents are desperately needed. As one of the largest classes of plant secondary metabolite, flavonoids can be widely found in various parts of the plant, and their antibacterial activities have been increasingly paid attention to. Based on the physicochemical parameters and antibacterial activities of sixty-six flavonoids reported, two regression equations between their ACD/LogP or LogD and their minimum inhibitory concentrations (MICs) to gram-positive bacteria were established with the correlation coefficients above 0.93, and then were verified by another sixty-eight flavonoids reported. From these two equations, the MICs of most flavonoids against gram-positive bacteria could be roughly calculated from their ACD/LogP or LogD, and the minimum MIC was predicted as approximately 10.2 or 4.8 μM, more likely falls into the range from 2.6 to 10.2 μM, or from 1.2 to 4.8 μM. Simultaneously, both tendentiously concave regression curves indicated that the lipophilicity is a key factor for flavonoids against gram-positive bacteria. Combined with the literature analyses, the results also suggested that the cell membrane is the main site of flavonoids acting on gram-positive bacteria, and which likely involves the damage of phospholipid bilayers, the inhibition of the respiratory chain or the ATP synthesis, or some others.
抗菌药物耐药性严重威胁人类健康，急需新型抗菌药物。黄酮类化合物作为植物次生代谢产物中最大的一类，广泛存在于植物的各个部位，其抗菌活性日益受到关注。基于 66 种黄酮类化合物的理化参数和抗菌活性数据，建立了它们的 ACD/LogP 或 LogD 与对革兰氏阳性菌最小抑菌浓度（MIC）之间的两个回归方程，相关系数均在 0.93 以上，并通过另外 68 种黄酮类化合物进行了验证。根据这两个方程，可以从黄酮类化合物的 ACD/LogP 或 LogD 大致估算出它们对革兰氏阳性菌的 MIC，最小 MIC 预测约为 10.2 或 4.8 μM，更可能落在 2.6 到 10.2 μM 或 1.2 到 4.8 μM 的范围内。同时，两条趋向凹形的回归曲线表明，亲脂性是黄酮类化合物对革兰氏阳性菌的关键因素。结合文献分析，结果还表明细胞膜是黄酮类化合物作用于革兰氏阳性菌的主要部位，可能涉及破坏磷脂双层、抑制呼吸链或 ATP 合成，或者其他一些机制。
