title: Synthesis and biological evaluation of 2-(alkoxycarbonyl)-3-anilinobenzo[b]thiophenes and thieno[2,3-b]pyridines as new potent anticancer agents.
abstract: Two new series of inhibitors of tubulin polymerization based on the 2-(alkoxycarbonyl)-3-(3',4',5'-trimethoxyanilino)benzo[b]thiophene and thieno[2,3-b]pyridine molecular skeletons were synthesized and evaluated for antiproliferative activity on a panel of cancer cell lines, inhibition of tubulin polymerization, cell cycle effects, and in vivo potency. Antiproliferative activity was strongly dependent on the position of the methyl group on the benzene portion of the benzo[b]thiophene nucleus, with the greatest activity observed when the methyl was located at the C-6 position. Also, in the smaller thieno[2,3-b]pyridine series, the introduction of the methyl group at the C-6 position resulted in improvement of antiproliferative activity to the nanomolar level. The most active compounds (4i and 4n) did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. Compound 4i significantly inhibited in vivo the growth of a syngeneic hepatocellular carcinoma in Balb/c mice.
authors: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44121 Ferrara, Italy. rmr@unife.it
authors: Romeo
authors: R
authors: Romagnoli
authors: Pier Giovanni
authors: PG
authors: Baraldi
authors: Maria
authors: M
authors: Kimatrai Salvador
authors: Delia
authors: D
authors: Preti
authors: Mojgan
authors: M
authors: Aghazadeh Tabrizi
authors: Marcella
authors: M
authors: Bassetto
authors: Andrea
authors: A
authors: Brancale
authors: Ernest
authors: E
authors: Hamel
authors: Ignazio
authors: I
authors: Castagliuolo
authors: Roberta
authors: R
authors: Bortolozzi
authors: Giuseppe
authors: G
authors: Basso
authors: Giampietro
authors: G
authors: Viola
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003078:Colchicine / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D008958:Models, Molecular; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D011725:Pyridines; D013876:Thiophenes; D014404:Tubulin; D003078:Colchicine