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

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

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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