Synthesis and antibacterial activities of a novel alkylide: 3-O-(3-aryl-2-propargyl) and 3-O-(3-aryl-2-propenyl)clarithromycin derivatives

Jian-Hua Liang; Yue-Ying Wang; He Wang; Xiao-Li Li; Kun An; Ying-Chun Xu; Guo-Wei Yao

doi:10.1016/j.bmcl.2010.03.038

Synthesis and antibacterial activities of a novel alkylide: 3-O-(3-aryl-2-propargyl) and 3-O-(3-aryl-2-propenyl)clarithromycin derivatives

Bioorg Med Chem Lett. 2010 May 1;20(9):2880-3. doi: 10.1016/j.bmcl.2010.03.038. Epub 2010 Mar 11.

Authors

Jian-Hua Liang¹, Yue-Ying Wang, He Wang, Xiao-Li Li, Kun An, Ying-Chun Xu, Guo-Wei Yao

Affiliation

¹ School of Life Science, Beijing Institute of Technology, Beijing 100081, China. ljhbit@bit.edu.cn

PMID: 20356738
DOI: 10.1016/j.bmcl.2010.03.038

Abstract

A series of novel 3-O-(3-aryl-E-2-propenyl)clarithromycin derivatives 8 and 3-O-(3-aryl-2-propargyl)clarithromycin derivatives 11 were designed, synthesized, and evaluated for their in vitro antibacterial activities. Compared with 8c and 11c (Ar was 5-pyrimidyl), 3-O-(3-(5'-pyrimidyl)-Z-1-propenyl) counterpart 6c displayed 4- to 64-fold more potent activities against erythromycin-susceptible Staphylococcus aureus and Streptococcus pneumoniae. Moreover, the activities of 6c, 8c, and 11c against erythromycin-resistant S. aureus and S. pneumoniae were in general 4-fold higher than those of the reference compound, clarithromycin and azithromycin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Clarithromycin / analogs & derivatives*
Clarithromycin / chemical synthesis
Clarithromycin / pharmacology
Microbial Sensitivity Tests
Staphylococcus aureus / drug effects
Streptococcus pneumoniae / drug effects
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Clarithromycin