title: Synthesis, antimitotic and antivascular activity of 1-(3',4',5'-trimethoxybenzoyl)-3-arylamino-5-amino-1,2,4-triazoles.
abstract: A new class of compounds that incorporated the structural motif of the 1-(3',4',5'-trimethoxtbenzoyl)-3-arylamino-5-amino-1,2,4-triazole molecular skeleton was synthesized and evaluated for their antiproliferative activity in vitro, interactions with tubulin, and cell cycle effects. The most active agent, 3c, was evaluated for antitumor activity in vivo. Structure-activity relationships were elucidated with various substituents on the phenyl ring of the anilino moiety at the C-3 position of the 1,2,4-triazole ring. The best results for inhibition of cancer cell growth were obtained with the p-Me, m,p-diMe, and p-Et phenyl derivatives 3c, 3e, and 3f, respectively, and overall, these compounds were more or less as active as CA-4. Their vascular disrupting activity was evaluated in HUVEC cells, with compound 3c showing activity comparable with that of CA-4. Compound 3c almost eliminated the growth of syngeneic hepatocellular carcinoma in Balb/c mice, suggesting that 3c could be a new antimitotic agent with clinical potential.
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara , Ferrara, Italy.
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Maria Kimatrai
authors.initials: MK
authors.lastname: Salvador
authors.forename: Filippo
authors.initials: F
authors.lastname: Prencipe
authors.forename: Valerio
authors.initials: V
authors.lastname: Bertolasi
authors.forename: Michela
authors.initials: M
authors.lastname: Cancellieri
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.forename: Francesca
authors.initials: F
authors.lastname: Consolaro
authors.forename: Elena
authors.initials: E
authors.lastname: Porcù
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Giampietro
authors.initials: G
authors.lastname: Viola
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells; D011485:Protein Binding; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000595013:(3-(4-tolylamino)-5-amino-1H-1,2,4-triazol-1-yl)(3,4,5-trimethoxyphenyl)methanone; D020533:Angiogenesis Inhibitors; D000814:Aniline Compounds; D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D014227:Triazines; D014230:Triazoles; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine