Anti-Helicobacter pylori activities of 9-substituted palmatine derivatives
10.16438/j.0513-4870.2020-0085
- VernacularTitle:9-取代巴马汀衍生物抗幽门螺杆菌活性研究
- Author:
Tian-yun FAN
1
;
Jing PANG
1
;
Qing-xuan ZENG
1
;
Yan-xiang WANG
2
;
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
2. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
9-substitute palmatine;
italic>Helicobacter pylori;
structure-activity relationship;
molecular docking
- From:
Acta Pharmaceutica Sinica
2020;55(6):1237-1244
- CountryChina
- Language:Chinese
-
Abstract:
Fifteen 9-substituted palmatine (1) derivatives were synthesized and evaluated for their anti-Helicobacter pylori (Hp) activities in vitro. Structure-activity relationship studies revealed that introducing appropriate substituted secondary amino group at position 9 of lead 1 might be beneficial for potency. Among them, compound 5a showed the most potential activity against metronidazole (Met) resistant Hp isolates with minimal inhibitory concentrations (MICs) of 4 μg·mL-1, much better than that of lead 1. Compound 5a displayed satisfactory safety profile in acute toxicity assay. Molecular docking suggested that 5a might act on Hp urease. The results provided key scientific evidence for the development of 1 derivatives into a new class of anti-Hp component.
