title: Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization.
abstract: Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy.
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Maria Dora
authors.initials: MD
authors.lastname: Carrion
authors.forename: Carlota
authors.initials: C
authors.lastname: Lopez Cara
authors.forename: Delia
authors.initials: D
authors.lastname: Preti
authors.forename: Francesca
authors.initials: F
authors.lastname: Fruttarolo
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Pavani
authors.forename: Mojgan Aghazadeh
authors.initials: MA
authors.lastname: Tabrizi
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Cristina
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: John A
authors.initials: JA
authors.lastname: Hadfield
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
mesh_terms: D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D011485:Protein Binding; D011869:Radioligand Assay; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C520651:2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo(b)thiophene; D050256:Antimitotic Agents; D013876:Thiophenes; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine