Design, synthesis, and antibacterial activity of pleuromutilin derivatives

Author:

Liu Hui‐xian1,Yao Wen‐yu2,Cui Ge3,Zhou Jing1,Yan Hao1,Guo Hui1,Wang Yu‐wei1ORCID,Zhang Yue345

Affiliation:

1. College of Pharmacy, Shaanxi University of Chinese Medicine Xianyang PR China

2. Jinan University College of Pharmacy Guangzhou PR China

3. School of Chemical and Pharmaceutical Engineering Hebei University of Science and Technology Shijiazhuang PR China

4. Hebei Research Center of Pharmaceutical and Chemical Engineering Shijiazhuang PR China

5. Hebei Province Key Laboratory of Molecular Chemistry for Drug Shijiazhuang PR China

Abstract

AbstractThis paper reports the design, synthesis, and antibacterial activity study of pleuromutilin derivatives with 2‐methyl‐4‐nitroaniline and 2‐methoxy‐4‐nitroaniline side chains at the C22 position. The structures of the new compounds were characterized by 1H‐NMR, 13C‐NMR and HRMS. The inhibitory activity of the compounds against MSSA, pyogeniccoccus, streptococcus, and MRSA strains was determined using the micro broth dilution method. The results showed that the compounds exhibited certain activity against Gram‐positive bacteria, among which compounds A8a, A8b, A8c, A8d, and A7 demonstrated superior antibacterial activity against MSSA, MRSA, and pyogeniccoccus compared to tiamulin, although the derivatives showed lower antibacterial activity against streptococcus compared to the control drug. Based on the favorable in vitro activity of A8c, the time‐kill kinetics against MRSA were evaluated, revealing that compound A8c could inhibit bacterial proliferation in a concentration‐dependent manner.

Publisher

Wiley

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