title: Nitroimidazoles, part 2: Synthesis, antiviral and antitumor activity of new 4-nitroimidazoles.
abstract: A series of 5-alkylamino and 5-alkylsulfanyl derivatives of 1-aryl-2-alkyl-4-nitro-1H-imidazoles 12-21, 31, and 34 were synthesized by a simple method with the aim to develop novel HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs). All the new compounds were tested against HIV-1 and HIV-2 in MT-4 cells. Compound 21, with an arylsulfanyl group at C(5) of the 4-nitro-1H-imidazole backbone showed an EC(50) value of 0.22 microg/ml against HIV-1 with a therapeutic index of 13. This means that compound 21 was cytotoxic to MT-4 cells at a CC(50) value of 2.57 microg/ml; also compounds 8, 22-25, 28, and 29 were cytotoxic to MT-4 cells within the 0.4-4 microg/ml concentration range. Compounds 8, and 12-21 were evaluated, as a rule, but found inactive at non-toxic concentrations against hepatitis C virus, herpes simplex type 1 and 2, cytomegalovirus (CMV), varicella-zoster virus (VZV), vaccinia virus, and vesicular stomatitis virus, and a number of other viruses. Yet, the therapeutic index of compounds 17 and 21 for CMV and VZV approached the tenfold cut-off point. Compounds 8 and 21 exhibited some cytostatic activity against leukemia and melanoma cell lines.
authors.affiliation: Fachbereich Chemie, Universität Konstanz, Postfach 5560, D-78457 Konstanz. info@al-masoudi.de
authors.forename: Najim A
authors.initials: NA
authors.lastname: Al-Masoudi
authors.forename: Yaseen A
authors.initials: YA
authors.lastname: Al-Soud
authors.forename: Aris
authors.initials: A
authors.lastname: Kalogerakis
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003587:Cytomegalovirus / Q000187:drug effects; D006678:HIV / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009593:Nitroimidazoles