6533b832fe1ef96bd129ae1b

RESEARCH PRODUCT

Synthesis, antiproliferative activity, and in silico insights of new 3-benzoylamino-benzo[ b ]thiophene derivatives

Anna Maria AlmericoCarla GentileAntonino LauriaFrancesco MingoiaAntonio Palumbo PiccionelloAnnamaria MartoranaUgo PerriconeAndrea PaceRoberta BartolottaAlessio Terenzi

subject

thiopheneVLAK protocolStereochemistryIn silicoCellAntineoplastic AgentsMechanism of actionHeLa CellHeLaAntineoplastic AgentStructure-Activity Relationship3-Benzoylamino-5-imidazol-4-yl-benzo[b]Settore BIO/10 - BiochimicaDrug DiscoverymedicineHumansMoietyComputer SimulationMitosisCell ProliferationPharmacologyAntitumor agentsbiologyDose-Response Relationship DrugMolecular StructureChemistryDrug Discovery3003 Pharmaceutical ScienceMedicine (all)Cell CycleOrganic ChemistryAntitumor agentG2/M phaseGeneral MedicineSettore CHIM/06 - Chimica OrganicaHeLa cell linebiology.organism_classificationSettore CHIM/08 - Chimica Farmaceuticamedicine.anatomical_structureCell cultureSettore CHIM/03 - Chimica Generale E InorganicathiophenesAntimitotic AgentTopoisomerase-II InhibitorDrug Screening Assays AntitumorHeLa CellsHuman

description

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.

yearjournalcountryeditionlanguage
2014-10-27
10.1016/j.ejmech.2014.12.002https://dx.doi.org/10.1016/j.ejmech.2014.12.002