Work

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

Year: 2024

Type: article

Abstract: 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.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.4c00458