Design, synthesis and antituberculosis activity of 2-aryl substituted benzothiopyranone compounds
10.16438/j.0513-4870.2023-1380
- VernacularTitle:2-芳基取代苯并硫代吡喃酮类化合物的设计、合成及其抗结核活性研究
- Author:
Xia-xia TANG
1
;
Wen-yi LI
1
;
Peng LI
1
;
Bin WANG
2
;
Yu LU
2
;
Hai-hong HUANG
1
;
Gang LI
1
Author Information
1. Chinese Academy of Medical Sciences Key Laboratory of Anti-DR TB Innovative Drug Research, Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
2. Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
- Publication Type:Research Article
- Keywords:
2-aryl substituted benzothiopyranone;
esign and synthesis;
antituberculosis activity;
preliminary druggability evaluation
- From:
Acta Pharmaceutica Sinica
2024;59(4):987-996
- CountryChina
- Language:Chinese
-
Abstract:
A novel series of 2-aryl substituted benzothiopyranone compounds was designed and synthesized based on our previously obtained benzothiopyranone scaffold with significant antituberculosis activity. All target compounds were evaluated for their antimycobacterial activity and preliminary druggability was subsequently investigated for some selected compounds with good activity. The results indicated that most compounds showed good activity against Mycobacterium tuberculosis H37Rv. Among them, compounds 8g, 8h, 8q and 9f showed potent activity with MIC ranged from 0.2 to 0.4 μg·mL-1. Furthermore, some active compounds exhibited low cytotoxicity and cardiotoxicity risk. It is worth noting that compounds 8h and 8q with good liver microsome stability and low inhibition of CYPs 3A4/5 and 2C9 were suitable for combination drug regimen to treat tuberculosis.
