Title:Synthesis and In Vitro anti-HCV and Antitumor Evaluation of Schisandronic Acid Derivatives
Volume: 17
Issue: 9
Author(s): Kai-Xia Zhang, Xi-Jing Qian, Wei Zheng, Meng-Cheng Cai, Ying Ma, Da-Zhi Zhang, Shi-Chong Yu, Qing-Guo Meng*Yong-Sheng Jin*
Affiliation:
- School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005,China
- School of Pharmacy, Second Military Medical University, Shanghai, 200433,China
Keywords:
Triterpenoids, schisandronic acid, anti-HCV activity, antitumor activity, SAR, synthesis.
Abstract:
Background: Schisandronic acid (SA), a triterpenoid from fruits of Schisandra sphenanthera,
inhibited pan-genotypic HCV entry into human hepatocytes by interfering with virion-cell
membrane fusion. It was a promising lead compound for the development of novel HCV entry inhibition
agents.
Objective: The aim of the present study is to search for compounds with more potent anti-HCV and
antitumor activities and explore SARs. A series of novel derivatives of SA were designed and synthesized
and evaluated for in vitro, their anti-HCV and antitumor activities.
Methods: SA derivatives were synthesized by reduction, condensation, esterification or amidation.
The anti-HCV activity of title compounds was tested by inhibition on HCVcc infection of Huh7
cells, and a preliminary MOA study was conducted by determining inhibition on HCVpp entry into
Huh7 cells. The antitumor activity in vitro was determined by MTT methods.
Results: In total, 24 novel derivatives were synthesized. Most of the compounds inhibited HCVcc
infection. Compounds 5h and 6 showed the most potent anti-HCVcc activities and inhibition of
HCVpp entry into Huh7 cells without obvious cytotoxicity. Most of the title compounds showed potent
in vitro antitumor activities against Bel7404 and SMMC7721 tumor cell lines. Compounds 5j
and 6 exhibited more potent antitumor activity than positive control SA and DOX.
Conclusion: Structural modification of SA could lead to the discovery of potent anti-HCV or antitumor
agents. Compounds 5h, 5j and 6 were promising lead compounds for development of novel HCV
entry inhibition or antitumor agents.
