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  2. Design and Synthesis of Cajanine Analogues against Hepatitis C Virus through Down-Regulating Host Chondroitin Sulfate N-Acetylgalactosaminyltransferase 1

Design and Synthesis of Cajanine Analogues against Hepatitis C Virus through Down-Regulating Host Chondroitin Sulfate N-Acetylgalactosaminyltransferase 1

  • J Med Chem. 2016 Nov 23;59(22):10268-10284. doi: 10.1021/acs.jmedchem.6b01301.
Xing-Yue Ji 1 Jin-Hua Chen 1 Guang-Hui Zheng 1 Meng-Hao Huang 1 Lei Zhang 1 Hong Yi 1 Jie Jin 1 Jian-Dong Jiang 1 Zong-Gen Peng 1 Zhuo-Rong Li 1
Affiliations

Affiliation

  • 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College , No. 1, Tiantan Xili, Beijing 100050, China.
Abstract

There still remains a need to develop new anti-HCV agents with distinct mechanism of action (MOA) due to the occurrence of resistance to direct-acting Antiviral agents (DAAs). Cajanine, a stilbenic component isolated from Cajanus cajan L., was identified as a potent HCV Inhibitor by phenotypic screening in this work (EC50 = 3.17 ± 0.75 μM). The intensive structure optimization provided significant insights into the structure-activity relationships. Furthermore, the MOA study revealed that cajanine inhibited HCV replications via down-regulating a cellular protein chondroitin sulfate N-acetylgalactosaminyltransferase 1. In consistency with this host-targeting mechanism, cajanine showed the similar magnitude of inhibitory activity against both drug-resistant and wild-type HCV and synergistically inhibited HCV replication with approved DAAs. Taken together, our study not only presented cajanine derivatives as a novel class of anti-HCV agents but also discovered a promising anti-HCV target to combat drug resistance.

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