title: Prenylated derivatives of baicalein and 3,7-dihydroxyflavone: synthesis and study of their effects on tumor cell lines growth, cell cycle and apoptosis.
abstract: Fourteen baicalein and 3,7-dihydroxyflavone derivatives were synthesized and evaluated for their inhibitory activity against the in vitro growth of three human tumor cell lines. The synthetic approaches were based on the reaction with prenyl or geranyl bromide in alkaline medium, followed by cyclization of the respective monoprenylated derivative. Dihydropyranoflavonoids were also obtained by one-pot synthesis, using Montmorillonite K10 clay as catalyst combined with microwave irradiation. In vitro screening of the compounds for cell growth inhibitory activity revealed that the presence of one geranyl group was associated with a remarkable increase in the inhibitory activity. Moreover, for the 3,7-dihydroxyflavone derivatives a marked increase in growth inhibitory effect was also observed for compounds with furan and pyran fused rings. The most active compounds were also studied regarding their effect on cell cycle profile and induction of apoptosis. Overall the results point to the relevant role of the prenylation of flavone scaffold in the growth inhibitory activity of cancer cells.
authors.affiliation: Centro de Química Medicinal da Universidade do Porto (CEQUIMED-UP), Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha 164, 4050-047 Porto, Portugal.
authors.forename: Marta Perro
authors.initials: MP
authors.lastname: Neves
authors.forename: Honorina
authors.initials: H
authors.lastname: Cidade
authors.forename: Madalena
authors.initials: M
authors.lastname: Pinto
authors.forename: Artur M S
authors.initials: AM
authors.lastname: Silva
authors.forename: Luís
authors.initials: L
authors.lastname: Gales
authors.forename: Ana Margarida
authors.initials: AM
authors.lastname: Damas
authors.forename: Raquel T
authors.initials: RT
authors.lastname: Lima
authors.forename: M Helena
authors.initials: MH
authors.lastname: Vasconcelos
authors.forename: Maria
authors.initials: M
authors.lastname: de São José Nascimento
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D044950:Flavanones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D005419:Flavonoids; C006680:baicalein; C422925:3,7-dihydroxyflavone