Synthesis and biological evaluation of novel tricyclic matrinic derivatives as potential anti-filovirus agents

Xin Zhang; Qiang Liu; Qianqian Li; Yinghong Li; Zhandong Liu; Hongbin Deng; Sheng Tang; Yanxiang Wang; Youchun Wang; Danqing Song

Acta Pharmaceutica Sinica B (Jul 2018)

Synthesis and biological evaluation of novel tricyclic matrinic derivatives as potential anti-filovirus agents

Xin Zhang,
Qiang Liu,
Qianqian Li,
Yinghong Li,
Zhandong Liu,
Hongbin Deng,
Sheng Tang,
Yanxiang Wang,
Youchun Wang,
Danqing Song

Affiliations

Xin Zhang: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 10050, China
Qiang Liu: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 102629, China
Qianqian Li: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 102629, China
Yinghong Li: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 10050, China
Zhandong Liu: Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Hongbin Deng: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 10050, China
Sheng Tang: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 10050, China
Yanxiang Wang: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 10050, China
Youchun Wang: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 102629, China; Corresponding authors.
Danqing Song: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 10050, China; Corresponding authors.

Journal volume & issue: Vol. 8, no. 4
pp. 629 – 638

Abstract

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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) 12N-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 7d exhibited the most potent potency against EBOV with an IC50 value of 5.29 μmol/L and an SI value of over 37.8. Further in vivo anti-EBOV assay of 7d identified its high effectiveness, and in vivo anti-MARV assay of 7d 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. KEY WORDS: Sophoridinic, Matrinic, Structure−activity relationship, EBOV, Filovirus

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b

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