title: Synthesis, antiproliferative activity, and in silico insights of new 3-benzoylamino-benzo[b]thiophene derivatives.
abstract: A new series of 3-benzoylamino-5-imidazol-5-yl-benzo[b]thiophenes and the parent amino derivatives were synthesized and screened as antitumor agents. All tested compounds showed concentration-dependent antiproliferative activity profile against HeLa cell line, exhibiting GI50 values in the low micromolar range. The most active compounds were tested in cell cycle perturbation experiments. A rapid accumulation of cells in the G2/M phase, with a concomitant reduction of cells in both the S and G0/G1 phases, was observed, suggesting that cell exposure to selected derivatives produces mitotic failure. To rationalize the biological results, the 3-benzoylamino-benzo[b]thiophenes were analyzed through the in silico VLAK protocol. Compounds presenting the 3,4,5-trimethoxy-benzoyl moiety were in silico classified as potential antimitotic agents or topoisomerase II inhibitors, in good agreement with the biological studies.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF" - Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Martorana
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF" - Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Gentile
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF" - Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Perricone
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF" - Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Antonio Palumbo
authors.initials: AP
authors.lastname: Piccionello
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF" - Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bartolotta
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF" - Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Terenzi
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF" - Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.affiliation: Istituto per lo Studio dei Materiali Nanostrutturati, (ISMN), Consiglio nazionale delle Ricerche (CNR), Via U. La Malfa 153, 90146 Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mingoia
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF" - Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Almerico
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF" - Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy. Electronic address: antonino.lauria@unipa.it.
authors.forename: Antonino
authors.initials: A
authors.lastname: Lauria
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000601782:3-benzoylamino-benzo(b)thiophene; D000970:Antineoplastic Agents; D013876:Thiophenes
keywords: 3-Benzoylamino-5-imidazol-4-yl-benzo[b]thiophenes; Antitumor agents; G2/M phase; HeLa cell line; Mechanism of action; VLAK protocol