Synthesis and In Vitro anti-HCV and Antitumor Evaluation of Schisandronic Acid Derivatives

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.

Cite this article as:

Zhang Kai-Xia , Qian Xi-Jing , Zheng Wei , Cai Meng-Cheng , Ma Ying , Zhang Da-Zhi , Yu Shi-Chong , Meng Qing-Guo *, Jin Yong-Sheng *, Synthesis and In Vitro anti-HCV and Antitumor Evaluation of Schisandronic Acid Derivatives, Medicinal Chemistry 2021; 17 (9) . https://dx.doi.org/10.2174/1573406416999200818150053