Ye Lianbao, Lin Pengfei, Du Wenjun, Wang Yuanyuan, Tang Chunping, Shen Zhibin
School of Pharmacy, Key Laboratory of New Drug Discovery and Evaluation of Ordinary Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou, China.
School of Traditional Chinese Medicine, Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou, China.
Front Microbiol. 2018 Nov 2;9:2262. doi: 10.3389/fmicb.2018.02262. eCollection 2018.
In this study a variety of phloroglucinols were isolated from the plant, and the activity experiment showed that the phloroglucinols had strong antifungal activity, especially methylphloroglucinol derivatives such as aspidin PB, dryofragin, aspidinol, aspidin BB, aspidin AB, and albicanol, in which the hydroxyl group of methylphloroglucinol is the active group of compounds, and C-2 or C-6 is the active site. The introduction of different groups in this position could change the properties and bioactivity of the compounds. In this study, different functional groups were introduced to the structure of methylphloroglucinol to obtain methylphloroglucinol derivatives that were synthesized, and antidermatophyte activities on , and were evaluated. Molecular docking verified its ability to combine the protein binding site. The antidermatophyte mechanism of compounds on cytochrome P450 sterol 14a-demethylase, squalene epoxidase, and β-1,3-glucan synthase was investigated by the enzyme-linked immunosorbent assay. The results showed that compounds had an inhibitory effect on four kinds of common dermatophytes in varying degrees, in which compound had the strongest activities, the binding mode of methylphloroglucinol and its derivatives were similar to those of three enzymes, and compounds and had significant effects on the activity of the three enzymes, and compound had a slightly stronger effect than the blank group. Compounds and also had a significant effect on the ergosterol synthesis of . This study could supply some antidermatophyte leading structure and possible mechanism for studying and developing new antifungal agents.
在本研究中，从该植物中分离出了多种间苯三酚，活性实验表明，间苯三酚具有较强的抗真菌活性，尤其是甲基间苯三酚衍生物，如绵马酚PB、绵马酸、绵马酚、绵马酚BB、绵马酚AB和白鲜醇，其中甲基间苯三酚的羟基是化合物的活性基团，C-2或C-6是活性位点。在该位置引入不同基团可改变化合物的性质和生物活性。本研究中，向甲基间苯三酚结构中引入不同官能团以获得合成的甲基间苯三酚衍生物，并对其对须发癣菌、红色毛癣菌和石膏样小孢子菌的抗皮肤癣菌活性进行了评估。分子对接验证了其与蛋白质结合位点结合的能力。通过酶联免疫吸附测定法研究了化合物对细胞色素P450甾醇14α-脱甲基酶、角鲨烯环氧酶和β-1,3-葡聚糖合酶的抗皮肤癣菌机制。结果表明，化合物对四种常见皮肤癣菌均有不同程度的抑制作用，其中化合物1活性最强，甲基间苯三酚及其衍生物的结合模式与三种酶的相似，化合物2和3对三种酶的活性有显著影响，化合物2的作用略强于空白组。化合物4和5对红色毛癣菌的麦角甾醇合成也有显著影响。本研究可为新型抗真菌药物的研究与开发提供一些抗皮肤癣菌的先导结构和可能机制。
