Novel Pleuromutilin Derivatives Conjugated with Phenyl-Sulfide and Boron-Containing Moieties as Potent Antibacterial Agents Against Antibiotic-Resistant Bacteria
Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC) - State Key Laboratory of Bioactive Substance and Function of Natural Medicines
In response to the escalating threat of microbial resistance, a series of novel pleuromutilin derivatives, conjugated with phenyl-sulfide and boron-containing moieties, were designed and synthesized. Most derivatives, especially 14b and 16b, demonstrated significant efficacy against Gram-positive bacteria, including multidrug-resistant strains, as well as pleuromutilin-resistant strains. Compound 16b displayed significantly bactericidal activity and low spontaneous resistance frequency as well as high stability in liver microsomes of rats and humans. Compound 16b also exhibited promising antibacterial activities and tolerance in mouse models. Our data highlight the potential of conjugated pleuromutilin derivatives as valuable agents against drug-resistant bacteria.
Luo, Xinyu and Wu, Guangxu and Feng, Jing and Zhang, Jie and Fu, Hengjian and Yu, Hang and Han, Zunsheng and Nie, Wansen and Zhu, Zihao and Liu, Bo and Pan, Weidong and Li, Beibei and Wang, Yan and Li, Tianlei and Zhang, Wenxuan and Wu, Song, Novel Pleuromutilin Derivatives Conjugated with Phenyl-Sulfide and Boron-Containing Moieties as Potent Antibacterial Agents Against Antibiotic-Resistant Bacteria. Available at SSRN: https://ssrn.com/abstract=4848340 or http://dx.doi.org/10.2139/ssrn.4848340
Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC) - State Key Laboratory of Bioactive Substance and Function of Natural Medicines ( email )
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