title: Arylazolyl(azinyl)thioacetanilide. Part 9: Synthesis and biological investigation of thiazolylthioacetamides derivatives as a novel class of potential antiviral agents.
abstract: In continuation of our endeavor to develop new, potent, selective and less toxic antiviral agents, a novel series of 2-(2-amino/chloro-4-(2,4-dibromophenyl) thiazol-5-ylthio)acetamide derivatives was synthesized via an expeditious route and evaluated for their anti-HIV activities against wild-type virus and clinically relevant mutant strains, and for their anti-influenza virus activities against influenza A (H1N1 and H3N2) and influenza B in cellular assays. The selected active compounds were also assayed for their enzymic inhibitory activities. The results showed that some 2-chloro substituted thiazolylthioacetamide derivatives possessed potent activity against wild type HIV-1 and several key mutant strains (E138K, K103N, L100I) of HIV-1 in MT-4 cells with EC(50) values in micromolar range. Two 2-amino substituted thiazole derivatives 8a7 and 8a8 displayed significant potency against influenza A/H1N1 in MDCK cells with EC(50) values much lower than that of oseltamivir carboxylate, ribavirin, amantadine and rimantadine. Though the mechanism of actions is still unclear, these novel thiazolylthioacetamides might serve as original leads for further pharmacological investigations as potential therapeutic agents against HIV-1 or influenza virus.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji'nan, ShanDong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Xuwang
authors.initials: X
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Ailin
authors.initials: A
authors.lastname: Liu
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002642:Chick Embryo; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000254:growth & development; D009981:Influenza B virus / Q000187:drug effects / Q000254:growth & development; D020128:Inhibitory Concentration 50; D061985:Madin Darby Canine Kidney Cells; D015394:Molecular Structure; D009154:Mutation; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013853:Thioacetamide / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D013853:Thioacetamide; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D009439:Neuraminidase