Synthesis and biological evaluation of novel tricyclic matrinic derivatives as potential anti-filovirus agents.
10.1016/j.apsb.2018.01.006
- Author:
Xin ZHANG
1
;
Qiang LIU
2
;
Qianqian LI
2
;
Yinghong LI
1
;
Zhandong LIU
3
;
Hongbin DENG
1
;
Sheng TANG
1
;
Yanxiang WANG
1
;
Youchun WANG
2
;
Danqing SONG
1
Author Information
1. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 10050, China.
2. Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 102629, China.
3. Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
EBOV;
Filovirus;
Matrinic;
Sophoridinic;
Structure−activity relationship
- From:
Acta Pharmaceutica Sinica B
2018;8(4):629-638
- CountryChina
- Language:English
-
Abstract:
Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus (EBOV) activities. Structure-activity relationship analysis indicated: (i) 12-dichlorobenzyl motif was beneficial for the activity; (ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound exhibited the most potent potency against EBOV with an IC value of 5.29 μmol/L and an SI value of over 37.8. Further anti-EBOV assay of identified its high effectiveness, and anti-MARV assay of suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.
