Design, synthesis and activity against drug-resistant bacteria evaluation of C-20, C-23 modified 5-O-mycaminosyltylonolide derivatives

  • Eur J Med Chem. 2022 Aug 5;238:114495. doi: 10.1016/j.ejmech.2022.114495.
Hongjin Zhai  1 ,  Chunying Luo  1 ,  Pu Yang  1 ,  Shuo Zhang  1 ,  Huanhuan Wang  1 ,  Yaquan Cao  1 ,  Yingxue Yang  1 ,  Haoyue Liu  1 ,  Xiaoyan Kong  1 ,  Firas Obald Arhema Frejat  1 ,  Changzhong Ren  2 ,  Xiufang Shi  3 ,  Chunli Wu  4
Affiliations
  • 1. 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.
  • 2. Henan Qunbo Pharmaceutical Research Institute Co. LTD, PR China.
  • 3. 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. Electronic address: [email protected].
  • 4. 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. Electronic address: [email protected].
PMID: 35675753 DOI: 10.1016/j.ejmech.2022.114495
Abstract

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.

Keywords
3-Quinoline; 5-O-Mycaminosyltylonolide; Antibacterial activity; Molecular docking; Synthesis; Tylosin.
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