Yimin Hu, Houguang Shi, Mingwei Zhou, Qingcheng Ren, Wei Zhu, Weixing Zhang, Zhiwei Zhang, Chengang Zhou, Yongqiang Liu, Xiao Ding, Hong C Shen, S Frank Yan, Fabian Dey, Waikwong Wu, Guanglei Zhai, Zheng Zhou, Zhiheng Xu, Ying Ji, Hua Lv, Tianyi Jiang, Wen Wang, Yunhua Xu, Maarten Vercruysse, Xiangyu Yao, Yi Mao, Xiaomin Yu, Kenneth Bradley, Xuefei Tan
The rise of multidrug resistant (MDR) Gram-negative (GN) pathogens and the decline of available antibiotics that can effectively treat these severe infections are a major threat to modern medicine. Developing novel antibiotics against MDR GN pathogens is particularly difficult as compounds have to permeate the GN double membrane, which has very different physicochemical properties, and have to circumvent a plethora of resistance mechanisms such as multiple efflux pumps and target modifications. The bacterial type II topoisomerases DNA gyrase (GyrA2 B2 ) and Topoisomerase IV (ParC2 E2 ) are highly conserved targets across all bacterial species and validated in the clinic by the fluoroquinolones...
September 10, 2020: Journal of Medicinal Chemistry