title: Synthesis, antiproliferative activity, and mechanism of action of a series of 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides.
abstract: 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Via Archirafi, 32, 90123 Palermo, Italy. demraffa@unipa.it
authors.forename: Demetrio
authors.initials: D
authors.lastname: Raffa
authors.forename: Benedetta
authors.initials: B
authors.lastname: Maggio
authors.forename: Fabiana
authors.initials: F
authors.lastname: Plescia
authors.forename: Stella
authors.initials: S
authors.lastname: Cascioferro
authors.forename: Salvatore
authors.initials: S
authors.lastname: Plescia
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: Raimondi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Daidone
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.forename: Antonietta
authors.initials: A
authors.lastname: Di Cristina
authors.forename: Rosaria Maria
authors.initials: RM
authors.lastname: Pipitone
authors.forename: Ruoli
authors.initials: R
authors.lastname: Bai
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D058105:Polymerization / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000737:chemistry
chemical_list: D000179:Acrylates; D000970:Antineoplastic Agents; D001549:Benzamides; D011725:Pyridines; D014404:Tubulin; D050257:Tubulin Modulators; D062367:ortho-Aminobenzoates; C023666:pyridine