title: (Z)-1-aryl-3-arylamino-2-propen-1-ones, highly active stimulators of tubulin polymerization: synthesis, structure-activity relationship (SAR), tubulin polymerization, and cell growth inhibition studies.
abstract: Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for antiproliferative activity in cell-based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI(50) values. Flow cytometry studies showed that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M block, these compounds caused microtubule stabilization like paclitaxel and induced apoptosis via activation of the caspase family. The observations made in this investigation demonstrate that (Z)-1-Aryl-3-arylamino-2-propen-1-one (10) represents a new class of microtubule-stabilizing agents.
authors.affiliation: Department of Oncological Sciences, Mount Sinai School of Medicine, Icahn Medical Institute, 1425 Madison Avenue, New York, New York 10029-6514, United States. r.reddy@mssm.edu
authors.forename: M V Ramana
authors.initials: MV
authors.lastname: Reddy
authors.forename: Balaiah
authors.initials: B
authors.lastname: Akula
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cosenza
authors.forename: Clement M
authors.initials: CM
authors.lastname: Lee
authors.forename: Muralidhar R
authors.initials: MR
authors.lastname: Mallireddigari
authors.forename: Venkat R
authors.initials: VR
authors.lastname: Pallela
authors.forename: D R C Venkata
authors.initials: DR
authors.lastname: Subbaiah
authors.forename: Andrew
authors.initials: A
authors.lastname: Udofa
authors.forename: E Premkumar
authors.initials: EP
authors.lastname: Reddy
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000627:Aminophenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D058105:Polymerization; D008941:Spindle Apparatus / Q000187:drug effects / Q000648:ultrastructure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C575279:1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one; D000475:Alkenes; D000627:Aminophenols; D000970:Antineoplastic Agents; D014404:Tubulin; D050257:Tubulin Modulators