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Design, Synthesis, and Activity Evaluation of C-23-Modified 5- O -Mycaminosyltylonolide Derivatives

2024; American Chemical Society; Volume: 15; Issue: 12 Linguagem: Inglês

10.1021/acsmedchemlett.4c00458

1948-5875

Zhengmin Fan, Zhaiwei Lin, Hongjin Zhai, Yaquan Cao, Huanhuan Wang, Aichata Maiga, Firas Obald Arhema Frejat, Changzhong Ren, Chunli Wu,

Pneumocystis jirovecii pneumonia detection and treatment

The widespread use of tylosin family drugs in clinical practice has led to bacterial resistance and reduced therapeutic efficacy. We designed and synthesized a series of new semisynthetic derivatives of tylosin with 5-O-mycaminosyltylonolide as the mother nucleus, mainly by introducing a variety of amino groups at its C-23 position. Some of the compounds showed high antibacterial activity against Gram-negative and Gram-positive bacteria. These findings indicate that the best compound, c9, possessed significant antibacterial activity (MIC = 0.5 ug/mL), excellent bactericidal efficacy, and a low induction rate of drug resistance against Staphylococcus aureus and Escherichia coli; it also showed good antibacterial activity against drug-resistant bacteria. In addition, compound c9 has a low toxicity in vitro and in vivo. In conclusion, compound c9 could be a potential antimicrobial lead compound that could also contribute to the development of macrolide antibiotics.