title: Design, synthesis and in vitro evaluation against human cancer cells of 5-methyl-5-styryl-2,5-dihydrofuran-2-ones, a new series of goniothalamin analogues.
abstract: The present work describes the preparation of a novel series of compounds based on the structure of goniothalamin (1), a natural styryl lactone with known cytotoxic and antiproliferative activities against a variety of cancer cell lines. A focused library of 17 goniothalamin analogues displaying the 5-methyl-2,5-dihydrofuran-2-one motif were prepared, and their cytotoxicity evaluated. While the analogues bearing methoxy and/or hydroxy groups on the aromatic moiety usually were at least three times less potent than the lead compound (1), ortho and para-trifluoromethyl analogues 10 and 11 exhibited levels of cytotoxicity similar to goniothalamin (1) against most cancer cell lines evaluated. One could suggest that the electronic effect of the trifluoromethyl group activates the inhibitor's electrophilic site via reduction of the electron density of the α,β-unsaturated ester oxygen atom. These results provide new information on the structure activity relationship of these α,β-unsaturated styryl lactones, thereby further focusing the design of novel candidates.
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, UNICAMP, CP 6154, Campinas, SP 13083-970, Brazil.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Bruder
authors.forename: Débora Barbosa
authors.initials: DB
authors.lastname: Vendramini-Costa
authors.forename: João Ernesto
authors.initials: JE
authors.lastname: de Carvalho
authors.forename: Ronaldo Aloise
authors.initials: RA
authors.lastname: Pilli
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D019073:HT29 Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D011753:Pyrones; C103280:goniothalamin; C039281:furan
keywords: 2,5-Dihydrofuran-2-ones; Antiproliferative activity; Cancer cells; Goniothalamin