Synthesis and biological evaluation of novel pleuromutilin derivatives with nitrogen-containing heterocycles as antibacterial agents.
- Author:
Xinyang WANG
;
Min CHEN
;
Duo WANG
;
Xiangdong CHEN
;
Yong LING
;
Xiaoli WANG
;
Hui WANG
- Publication Type:Journal Article
- From:
Acta Pharmaceutica Sinica
2015;50(10):1297-304
- CountryChina
- Language:Chinese
-
Abstract:
A series of new pleuromutilins derivatives were designed and synthesized through coupling 2-aminothiazole ring of WL001 with different nitrogen-containing substituted heterocycles in the side chain. Their biological activities were evaluated against both Gram-positive and Gram-negative clinical bacteria in vitro Most new compounds displayed specificity to certain strain of bacteria. Particularly, compounds with saturated nitrogen-containing heterocycles exhibited significant antibacterial activities (0.062 5-8 µg · mL(-1)) superior or similar to those of amoxicillin, tiamulin and levofloxcin. Furthermore, treatment with 15a and 15b having piperidine or morpholine residues also could effectively inhibit Gram-negative bacteria. Therefore, our novel findings may provide a new insight into the design of novel pleuromutilin derivatives and lay the basis for further studies on the treatment of drug-resistance of pathogenic bacteria.
