beta'-Hydroxy-alpha,beta-unsaturated ketones: A new pharmacophore for the design of anticancer drugs. Part 2.
Novel antiproliferative beta'-acyloxy-alpha,beta-unsaturated ketones were obtained by means of an iron(III)-catalyzed multicomponent domino process (ABB' 3CR). The most active derivatives displayed GI(50) values in the range of 0.5-3.9 muM against a panel of representative human solid tumor cell lines: A2780, SW1573, HBL-100, T-47D and WiDr. Analysis of cells following 24 h exposure to these drugs showed cell cycle arrest in the S and G(2)/M phase, in a dose-dependent manner. Our data indicate that the beta'-acyloxy-alpha,beta-unsaturated ketones cause permanent damage to the cells and induce apoptosis.
Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Universidad de la Laguna, C/ Astrofísico Francisco Sánchez, 2, 38206 La Laguna, Spain.
Leticia G
LG
León
Rubén M
RM
Carballo
María C
MC
Vega-Hernández
Pedro O
PO
Miranda
Víctor S
VS
Martín
Juan I
JI
Padrón
José M
JM
Padrón
D000475:Alkenes / Q000737:chemistry; D017304:Annexin A5 / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002712:Chlorides; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology*; D008956:Models, Chemical
D000475:Alkenes; D017304:Annexin A5; D000970:Antineoplastic Agents; D002712:Chlorides; D005290:Ferric Compounds; D007659:Ketones; C024555:ferric chloride