School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Department of Cosmetic Science, Providence University, Taichung 433, Taiwan.
Int J Mol Sci. 2019 Sep 14;20(18):4564. doi: 10.3390/ijms20184564.
resistance to current antibiotics has become the greatest global challenge facing public health. The development of new antimicrobial agents is urgent and important and is needed to provide additional therapeutic options. In our previous study, we found out that pterostilbene exhibited potent antibacterial activity, especially against methicillin-resistant (MRSA). According to previous studies, 1,2,3-triazole, with the characteristic of increasing the interaction with the target readily and enhancing water solubility, were widely used in the approved anti-bacterial drugs. Therefore, these results attract our interest to use the structure of pterostilbene as a scaffold for the hybrid 1,2,3-triazole moiety to develop a novel anti-MRSA infection agent. In this study, we demonstrated the design and synthesis of a series of triazolylpterostilbene derivatives. Among these compounds, compound exhibited the most potent anti-MRSA activity with a minimum inhibitory concentration (MIC) value of 1.2-2.4 μg/mL and a minimum bactericidal concentration (MBC) value of 19.5-39 μg/mL. The structure-activity relationship and antibacterial mechanism were investigated in this study. Molecular docking studies were carried out to verify and rationalize the biological results. In this study, the results confirmed that our design could successfully increase the inhibitory activity and specificity against MRSA. Compound could be used as a candidate for anti-bacterial agents and in depth vivo studies should be further investigated.
对现有抗生素的耐药性已成为全球公共卫生面临的最大挑战。开发新的抗菌药物迫在眉睫，十分重要，这将为治疗提供更多选择。在我们之前的研究中，我们发现紫檀芪表现出很强的抗菌活性，尤其是对耐甲氧西林金黄色葡萄球菌（MRSA）。根据之前的研究，1,2,3-三唑具有增加与靶标相互作用的易感性和增强水溶性的特点，被广泛应用于已批准的抗菌药物中。因此，这些结果引起了我们的兴趣，我们希望使用紫檀芪的结构作为支架，将 1,2,3-三唑部分进行杂交，从而开发出一种新型的抗耐甲氧西林金黄色葡萄球菌感染的药物。在这项研究中，我们设计并合成了一系列三唑基紫檀芪衍生物。在这些化合物中，化合物 表现出最强的抗 MRSA 活性，最小抑菌浓度（MIC）值为 1.2-2.4 μg/mL，最小杀菌浓度（MBC）值为 19.5-39 μg/mL。本研究还对构效关系和抗菌机制进行了探讨。分子对接研究进一步验证并合理化了生物学结果。在本研究中，结果证实我们的设计能够成功提高对 MRSA 的抑制活性和特异性。化合物 可作为候选抗菌药物，应进一步进行深入的体内研究。
