title: Synthesis and antiproliferative activity of 3-aryl-2-(1H-benzotriazol-1-yl)acrylonitriles. Part III.
abstract: A new series of 30 3-aryl-2-(1H-benzotriazol-1-yl)acrylonitriles were synthesized and tested for biological activity as part of our research in the antimicrobial and antitumor fields. In particular, title compounds were evaluated in vitro against representative strains of Gram-positive and Gram-negative bacteria (S. aureus, Salmonella spp), mycobacteria (M. fortuitum, M. smegmatis ATCC 19420 and M. tuberculosis ATCC 27294), yeast and mould (C. albicans ATCC 10231 and A. fumigatus). Furthermore, their antiretroviral activity against HIV-1 was determined in MT-4 cells together with cytotoxicity. In these assays title compounds and 47 additional derivatives described previously (P. Sanna, A. Carta, M.E. Rahbar Nikookar, Eur. J. Med. Chem. 35 (2000) 535-543; P. Sanna, A. Carta, L. Gherardini, M.E. Rahbar Nikookar, Farmaco 57 (2002) 79-87) were tested for their capability to prevent MT-4 cell growth. All compounds resulted devoid of antibacterial, antifungal and anti-HIV-1 activity. In anti-mycobacterial assays several compounds resulted active (MIC(50)=6.0-70 microM) against M. tuberculosis. However, since they showed cytotoxicity against MT-4 cells at lower concentrations (CC(50)=0.05-25 microM), their anti-mycobacterial activity was not selective. For this reason, the most cytotoxic compounds were also evaluated for antiproliferative activity against a panel of human cell lines derived from both hematological and solid tumors. Compound 34 resulted the most potent compound against the above human tumor-derived cell lines.
authors.affiliation: Dipartimento Farmaco-Chimico-Tossicologico, Università degli Studi di Sassari, Via Muroni 23/a, 07100, Sassari, Italy. acarta@ssmain.uniss.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Carta
authors.forename: Paolo
authors.initials: P
authors.lastname: Sanna
authors.forename: Michele
authors.initials: M
authors.lastname: Palomba
authors.forename: Laura
authors.initials: L
authors.lastname: Vargiu
authors.forename: Massimiliano
authors.initials: M
authors.lastname: La Colla
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
mesh_terms: D000181:Acrylonitrile / Q000031:analogs & derivatives*; D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D000181:Acrylonitrile