TSMU I.Kutateladze Institute of Pharmacochemistry, Tbilisi, 0159, Georgia.
Institute of Biomedical Chemistry, 10 bldg, 119121, Moscow, Russian Federation.
Curr Top Med Chem. 2019;19(4):292-304. doi: 10.2174/1568026619666190122152957.
Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity.
The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi.
In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method.
Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg).
Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents.
酚酸（咖啡酸、阿魏酸和对香豆酸）广泛分布于植物界，具有广泛的生物活性，包括抗菌活性。
本文的目的是合成一些基于计算机辅助预测选择的咖啡酸衍生物，并评估它们对革兰氏阳性和革兰氏阴性细菌以及一系列真菌的体外抗菌特性。
使用计算机辅助预测生物活性来鉴定最有前途的合成和生物测试结构，以及它们的抗菌作用的潜在机制。设计的化合物使用经典的有机合成方法合成。使用微量稀释法研究抗菌活性。
测试的 12 种化合物表现出良好的抗菌活性。在所测试的 12 种化合物中，有 5 种化合物的活性优于参考药物氨苄西林和链霉素。尽管所有化合物对测试的所有细菌都表现出良好的活性，但细菌对化合物的敏感性总体上有所不同。抗真菌活性评估表明，所有化合物均比酮康唑更具活性，而 7 种化合物（2、3、4、5、7、8 和 12）比比佛拉唑更具活性。对接结果表明，回旋酶抑制是抗菌作用的潜在机制，而 14α-去甲基酶抑制可能是抗真菌作用的原因。PROTOX 预测的细胞毒性表明，化合物没有毒性（LD50 为 1000-2000mg/kg）。
合成了 13 种化合物，其中 6 种为新化合物，并测试了 12 种化合物的抗菌活性。研究的化合物表现出有希望的高效且无毒的抗菌特性，可被视为新型药物制剂的先导化合物。
