用阳离子氯丙嗪-肽缀合物靶向多重耐药金黄色葡萄球菌。
Targeting multidrug resistant Staphylococcus aureus with cationic chlorpromazine-peptide conjugates.
作者信息
Panjla Apurva, Kaul Grace, Akhir Abdul, Saxena Deepanshi, Joshi Saurabh, Modak Chandrima, Kumari Dipti, Jain Alok, Chopra Sidharth, Verma Sandeep
机构信息
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, 208016, UP, India.
Department of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Sector 10, Sitapur Road, Janakipuram Extension, Lucknow, 226031, UP, India.
出版信息
Chem Asian J. 2023 May 16;18(10):e202300169. doi: 10.1002/asia.202300169. Epub 2023 Apr 26.
Antimicrobial resistance is a serious public health risk. Its severity is fueled on an unprecedented scale, necessitating the demand for novel antimicrobial scaffolds aimed at novel targets. Herein, we present cationic chlorpromazine peptide conjugates that are rationally intended to targetmultidrug-resistant (MDR) bacteria. The most potent compound, CPWL, of all the conjugates evaluated, showed promising antibacterial activity against clinical, MDR S. aureus, with no cytotoxicity. The molecular docking experiments confirmed that CPWL possessed a very high affinity for S. aureus enoyl reductase (saFabI). Furthermore, CPWL antibacterial action against saFabI was further corroborated by MD simulation studies. Thus, our findings highlight cationic chlorpromazine as a promising scaffold for the development of saFabI inhibitors to target severe staphylococcal infections.
抗菌耐药性是一个严重的公共卫生风险。其严重程度正以前所未有的规模加剧，因此需要针对新靶点的新型抗菌支架。在此，我们展示了阳离子氯丙嗪肽缀合物，其合理设计旨在靶向多重耐药（MDR）细菌。在所有评估的缀合物中，最有效的化合物CPWL对临床多重耐药金黄色葡萄球菌显示出有前景的抗菌活性，且无细胞毒性。分子对接实验证实CPWL对金黄色葡萄球菌烯酰还原酶（saFabI）具有非常高的亲和力。此外，MD模拟研究进一步证实了CPWL对saFabI的抗菌作用。因此，我们的研究结果突出了阳离子氯丙嗪作为开发靶向严重葡萄球菌感染的saFabI抑制剂的有前景的支架。
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