6533b85efe1ef96bd12c07d9

RESEARCH PRODUCT

Synthesis, antiproliferative activity, and mechanism of action of a series of 2-{[2E]-3-phenylprop-2-enoylamino}benzamides

Giuseppe DaidoneManlio TolomeoBenedetta MaggioErnest HamelAntonietta Di CristinaMaria Valeria RaimondiStella CascioferroSalvatore PlesciaRaffa DemetrioFabiana PlesciaRuoli BaiStefania GrimaudoMaria Rosaria Pipitone

subject

Pyridinesmedicine.drug_classStereochemistryAntineoplastic AgentsCarboxamideChemical synthesisArticlePolymerizationInhibitory Concentration 50Structure-Activity RelationshipTubulinCell Line TumorDrug DiscoverymedicineHumansStructure–activity relationshiportho-AminobenzoatesCytotoxicity2-{[2E]-3-phenylprop-2-enoylamino}benzamides antimitotic agents cytotoxic activityPharmacologyDose-Response Relationship DrugbiologyChemistryTubulin ModulatorsCell CycleOrganic ChemistryGeneral MedicineCell cycleSettore CHIM/08 - Chimica FarmaceuticaTubulin ModulatorsTubulinAcrylatesMechanism of actionBiochemistryBenzamidesbiology.proteinDrug Screening Assays Antitumormedicine.symptom

description

Several new 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides 12a–s and 17t–v were synthesized by stirring in pyridine the (E)-3-(2-R1-3-R2-4-R3-phenyl)acrylic acid chlorides 11c–k and 11t–v with the appropriate anthranilamide derivatives 10a–c or the 5-iodoanthranilic acid 13. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution for 17t, the most active of the series, indicate that these new antiproliferative compounds act as antitubulin agents.

yearjournalcountryeditionlanguage
2011-01-01
10.1016/j.ejmech.2011.03.067http://hdl.handle.net/10447/54204