title: Synthesis of methoxylated goniothalamin, aza-goniothalamin and γ-pyrones and their in vitro evaluation against human cancer cells.
abstract: The present work describes the preparation of three novel series of compounds based on the structure of goniothalamin, a natural styryl lactone which has been found to display cytotoxic and antiproliferative activities against a variety of cancer cell lines. A focused library of 29 novel goniothalamin analogues was prepared and evaluated against seven human cancer cell lines. While the γ-pyrones and the aza-goniothalamin analogues were less potent than the lead compound, 2,4-dimethoxy analogue 88 has shown to be more potent in vitro than goniothalamin against all cancer cell lines evaluated. Furthermore, it was more potent than doxorubicin against NCI-ADR/RES, OVCAR-03 and HT-29 while being less toxic to human keratinocytes (HaCat). The 3,5-dimethoxy analogue 90 and 2,4,5-trimethoxy analogue 92 also displayed promising antiproliferative activity when compared to goniothalamin (1). These results provide new elements for the design and synthesis of novel representatives of this family of natural compounds.
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, UNICAMP, CP 6154, 13083-970 Campinas, SP, Brazil.
authors.forename: Rosimeire Coura
authors.initials: RC
authors.lastname: Barcelos
authors.forename: Julio Cezar
authors.initials: JC
authors.lastname: Pastre
authors.forename: Vanessa
authors.initials: V
authors.lastname: Caixeta
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: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000494:pharmacology*; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
chemical_list: D011753:Pyrones; D054852:Small Molecule Libraries; C103280:goniothalamin; D004317:Doxorubicin