Synthesis and the biological evaluation of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles as potential anti-hepatitis B virus agents

• Published in: Antiviral research 2006-08, Vol.71 (1), p.7-14
• Main Authors: Tan, Theresa May Chin, Chen, Yu, Kong, Kah Hoe, Bai, Jing, Li, Yang, Lim, Seng Gee, Ang, Thiam Hong, Lam, Yulin
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral activity; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biological and medical sciences; DNA, Viral - chemistry; DNA, Viral - genetics; Hepatitis B e Antigens - biosynthesis; Hepatitis B Surface Antigens - biosynthesis; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - growth & development; Hepatitis B virus - metabolism; Hepatitis B virus-e antigen; Hepatitis B virus-s antigen; Hepatitis B, Chronic - drug therapy; Hepatocytes; Human viral diseases; Humans; Infectious diseases; Magnetic Resonance Spectroscopy; Medical sciences; Oxadiazoles; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Pharmacology. Drug treatments; Polymerase Chain Reaction; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared; Viral diseases; Viral hepatitis
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2006.02.007

Current treatments for chronic hepatitis B virus (HBV) infection include the use of interferon-α and of nucleoside analogs lamivudine, adefovir and entecavir. However, the use of interferon-α has many side effects while that of nucleosidic inhibitors can lead to the emergence of resistant viruses. Hence, new drugs for the treatment of HBV infection are still highly desired. Oxadiazoles have been observed to exhibit antiviral activities against RNA viruses. In this study, a facile synthesis of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles is reported. The compounds were then evaluated for their anti-HBV activity. 1-{2-[5-(1-Benzenesulfonyl-propyl)-[1,3,4]oxadiazol-2-yl-sulfanyl]-ethyl}-4-(2-methoxy-phenyl)-piperazine ( 1i) was able to inhibit the expression of the viral antigens, HBsAg and HBeAg in a concentration-dependent manner with no cytotoxic effects and without any effects on the expression of viral transcripts. Concentration- and time-dependent reductions in virion production were also observed. The inhibition of virion production was comparable to that of lamivudine and EC 50 values of 1.63 and 2.96 μM were obtained for compound 1i and lamivudine, respectively. Thus, in addition to the antiviral effects on RNA viruses, oxadiazoles also have anti-HBV activities.