Synthesis of hemslecin A derivatives: A new class of hepatitis B virus inhibitors

• Published in: Bioorganic & medicinal chemistry letters 2013-03, Vol.23 (5), p.1201-1205
• Main Authors: Guo, Rui-Hua, Geng, Chang-An, Huang, Xiao-Yan, Ma, Yun-Bao, Zhang, Quan, Wang, Li-Jun, Zhang, Xue-Mei, Zhang, Rong-Ping, Chen, Ji-Jun
• Format: Article
• Language: English
• Subjects: Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; chemistry; Cucurbitaceae - chemistry; Cucurbitacins - chemical synthesis; Cucurbitacins - pharmacology; Derivatives; DNA replication; DNA, Viral - isolation & purification; Hemslecin A; Hep G2 Cells; hepatitis B antigens; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Humans; inhibitory concentration 50; secretion; Structure-Activity Relationship; viruses
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.01.024

A series of hemslecin A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities, namely, inhibiting the secretion of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA replication on HepG 2.2.15 cells. Most of the derivatives showed enhanced anti-HBV activities, of which compounds A1–A7, B5, C and E exhibited significant activities inhibiting HBV DNA replication with IC50 values of 2.8–11.6μM, comparable to that of the positive control, tenofovir. Compounds A1–A3, A5, B5, and C displayed low cytotoxicities, which resulted in high SI values of 89.7, 55.6, 77.8, >83.4, >55.8, and >150.5, respectively.