International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou, 510632, PR China.
J Antibiot (Tokyo). 2020 Feb;73(2):82-90. doi: 10.1038/s41429-019-0257-x. Epub 2019 Nov 14.
Methicillin-resistant Staphylococcus aureus (MRSA) infection is a major threat to human health due to its resistance to almost all classes of antibiotics. Discovery of novel antibacterial agents with new structures which combat the pathogens responsible for MRSA is urgent. In this study, three series of benzyl phenyl sulfide derivatives were designed and synthesized, and their antibacterial activity against eleven MRSA strains were evaluated. The results showed that two series of the synthetic compounds (5a-5l and 12p-12u) exhibit potent antibacterial activity against S. aureus and MRSA, with minimum inhibitory concentrations of 2-64 μg/mL. The structure-activity relationships are discussed and the mechanism of the antibacterial activity was shown to involve the destruction of the bacterial cell membrane. Finally, the MTT assay results suggest that the toxicity of compounds 5f and 5h is selective between bacteria and mammalian cells.
耐甲氧西林金黄色葡萄球菌（MRSA）感染是对人类健康的主要威胁，因为它几乎对所有类别的抗生素都具有耐药性。发现具有新结构的新型抗菌剂来对抗导致 MRSA 的病原体是当务之急。在这项研究中，设计并合成了三系列苄基苯硫醚衍生物，并评估了它们对 11 株耐甲氧西林金黄色葡萄球菌的抗菌活性。结果表明，两个系列的合成化合物（5a-5l 和 12p-12u）对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌具有很强的抗菌活性，最小抑菌浓度为 2-64μg/mL。讨论了构效关系，抗菌活性的机制表明涉及破坏细菌细胞膜。最后，MTT 检测结果表明，化合物 5f 和 5h 的毒性在细菌和哺乳动物细胞之间具有选择性。
