Design, synthesis, and antibacterial activity of pleuromutilin derivatives

• Published in: Chemical biology & drug design 2024-06, Vol.103 (6), p.e14554-n/a
• Main Authors: Liu, Hui‐xian, Yao, Wen‐yu, Cui, Ge, Zhou, Jing, Yan, Hao, Guo, Hui, Wang, Yu‐wei, Zhang, Yue
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibiotics; derivatives; design; Diterpenes - chemical synthesis; Diterpenes - chemistry; Diterpenes - pharmacology; Drug Design; Gram-Positive Bacteria - drug effects; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; pleuromutilin; Pleuromutilins; Polycyclic Compounds - chemical synthesis; Polycyclic Compounds - chemistry; Polycyclic Compounds - pharmacology; Streptococcus - drug effects; Structure-Activity Relationship; synthesis
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.14554

This 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. We 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 inhibitory activity of the compounds against MSSA, pyogeniccoccus, streptococcus, and MRSA strains was determined. The results showed that the compounds exhibited certain activity against Gram‐positive bacteria.