Anti-MRSA activities of cycloberberine derivatives with a novel chemical scaffold
10.16438/j.0513-4870.2019-0485
- VernacularTitle:全新骨架环化小檗碱衍生物抗MRSA活性研究
- Author:
Tian-yun FAN
1
;
Yuan-shuai YANG
1
;
Xin-xin HU
1
;
Yan-xiang WANG
1
;
Xue-fu YOU
1
;
Dan-qing SONG
1
Author Information
1. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
cycloberberine;
antibacterial;
MRSA;
structure-activity relationship;
molecular dock
- From:
Acta Pharmaceutica Sinica
2019;54(9):1627-1635
- CountryChina
- Language:Chinese
-
Abstract:
Using CBBR as the parent core constructed in our lab, we designed and synthesized 15 novel compounds with diverse structures for evaluation of anti-bacterial activities. Structure activity relationship studies revealed that ① ring C was essential for the activity; ② 7,8- or 8,13-disubstituted CBBR derivatives showed ideal activities, weaker or similar to those corresponding to 7-, 8-, or 13-monosubstituted CBBR derivatives. Among those, compound 9a showed the most potential activity against MRSA/VISA isolates with MIC values of 1-2 μg·mL-1, much better than Lev. 9a also displayed higher stability in the plasma and liver microsomes. Molecular docking indicated that 9a might target bacterial DNA Topo IV ParE subunit, indicating a mode of action distinct from current antibacterial drugs on market. The results provided key scientific evidence for developing such compounds into a new family of anti-MRSA drugs.
