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; Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou, 450001, PR China.
Henan Qunbo Pharmaceutical Research Institute Co. LTD, PR China.
Eur J Med Chem. 2022 Aug 5;238:114495. doi: 10.1016/j.ejmech.2022.114495. Epub 2022 May 31.
With the increasing incidence of antibiotic resistance, there is an urgent need to develop new antibiotics with excellent activity against drug-resistant bacteria. Three novel series of tylosin semisynthetic derivatives were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. Among these derivatives, compound C-2 demonstrated potent antibacterial activity against both gram-positive and gram negative bacteria, and non mutagenic. More importantly, compound C-2 displayed high antimicrobial potency against Gram-positive bacteria in a murine model, and was found to be more efficient than tildipirosin. Thus, compound C-2 had great potential as a promising lead compound for the treatment of bacterial infection.
随着抗生素耐药性的不断增加，迫切需要开发对耐药菌具有优异活性的新型抗生素。设计、合成了三种新型泰乐菌素半合成衍生物系列，并评估了它们对各种革兰氏阳性菌和革兰氏阴性菌的抗菌活性。在这些衍生物中，化合物 C-2 对革兰氏阳性菌和革兰氏阴性菌均表现出很强的抗菌活性，且无致突变性。更重要的是，化合物 C-2 在小鼠模型中对革兰氏阳性菌显示出很高的抗菌效力，并且比替米考星更有效。因此，化合物 C-2 作为一种有前途的治疗细菌感染的先导化合物具有很大的潜力。
