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

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--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, , possessed significant antibacterial activity (MIC = 0.5 ug/mL), excellent bactericidal efficacy, and a low induction rate of drug resistance against and ; it also showed good antibacterial activity against drug-resistant bacteria. In addition, compound has a low toxicity in vitro and in vivo. In conclusion, compound could be a potential antimicrobial lead compound that could also contribute to the development of macrolide antibiotics.