Synthesis and the biological evaluation of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles as potential anti-hepatitis B virus agents. 2006

Theresa May Chin Tan, and Yu Chen, and Kah Hoe Kong, and Jing Bai, and Yang Li, and Seng Gee Lim, and Thiam Hong Ang, and Yulin Lam
Department of Biochemistry, National University of Singapore, Medical Drive, Singapore. bchtant@nus.edu.sg

Current treatments for chronic hepatitis B virus (HBV) infection include the use of interferon-alpha and of nucleoside analogs lamivudine, adefovir and entecavir. However, the use of interferon-alpha 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 microM were obtained for compound 1i and lamivudine, respectively. Thus, in addition to the antiviral effects on RNA viruses, oxadiazoles also have anti-HBV activities.

UI MeSH Term Description Entries
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D010069 Oxadiazoles Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms. Oxadiazole
D004279 DNA, Viral Deoxyribonucleic acid that makes up the genetic material of viruses. Viral DNA
D006513 Hepatitis B e Antigens A closely related group of antigens found in the plasma only during the infective phase of hepatitis B or in virulent chronic hepatitis B, probably indicating active virus replication; there are three subtypes which may exist in a complex with immunoglobulins G. HBeAg,Hepatitis B e Antigen,Hepatitis Be Antigen,e Antigen,e Antigens,HBe Ag-1,HBe Ag-2,Hepatitis Be Antigens,Antigen, Hepatitis Be,Antigen, e,Antigens, Hepatitis Be,Antigens, e,Be Antigen, Hepatitis,Be Antigens, Hepatitis
D006514 Hepatitis B Surface Antigens Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen. Australia Antigen,HBsAg,Hepatitis B Surface Antigen,Antigen, Australia
D006515 Hepatitis B virus The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum. Dane Particle,Hepatitis Virus, Homologous Serum,B virus, Hepatitis,Hepatitis B viruses,Particle, Dane,viruses, Hepatitis B
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D013055 Spectrophotometry, Infrared Spectrophotometry in the infrared region, usually for the purpose of chemical analysis through measurement of absorption spectra associated with rotational and vibrational energy levels of molecules. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) IR Spectra,Infrared Spectrophotometry,IR Spectras,Spectra, IR
D016133 Polymerase Chain Reaction In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain

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