Fan Zhengmin, Lin Ziwei, Zhai Hongjin, Cao Yaquan, Wang Huanhuan, Maiga Aichata, Frejat Firas Obald Arhema, Ren Changzhong, Wu Chun-Li
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
Key Laboratory of Technology of Drug Preparation, Zhengzhou University, Ministry of Education of China, Zhengzhou 450001, PR China.
ACS Med Chem Lett. 2024 Nov 25;15(12):2171-2180. doi: 10.1021/acsmedchemlett.4c00458. eCollection 2024 Dec 12.
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.
泰乐菌素类药物在临床实践中的广泛使用已导致细菌耐药性并降低了治疗效果。我们以5-麦考米诺糖泰乐菌素A为母核设计并合成了一系列新的泰乐菌素半合成衍生物，主要是在其C-23位引入各种氨基。其中一些化合物对革兰氏阴性菌和革兰氏阳性菌显示出高抗菌活性。这些发现表明，最佳化合物 具有显著的抗菌活性（MIC = 0.5μg/mL）、优异的杀菌效果以及对 和 的低耐药诱导率；它对耐药菌也显示出良好的抗菌活性。此外，化合物 在体外和体内均具有低毒性。总之，化合物 可能是一种潜在的抗菌先导化合物，也可能有助于大环内酯类抗生素的开发。
