RESUMO
Ten sesquiterpenoids (1-10), with a dihydro-beta-agarofuran skeleton, were isolated from Maytenus cuzcoina (Celastraceae). Their structures were elucidated on the basis of spectral analysis, including homo- and heteronuclear correlations NMR experiments (COSY, ROESY, HMQC and HMBC), and chemical correlations. The compounds have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. Compounds 1-3, 6 and 7 showed strong inhibitory effects on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA). Their structure-activity relationship is discussed.
Assuntos
Sesquiterpenos/farmacologia , Antígenos Virais/efeitos dos fármacos , Antígenos Virais/metabolismo , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Plantas Medicinais/química , Sesquiterpenos/análise , Sesquiterpenos/isolamento & purificação , Espectrofotometria , Relação Estrutura-Atividade , Acetato de Tetradecanoilforbol/farmacologia , Células Tumorais CultivadasRESUMO
The effects produced by nine dihydro-beta-agarofuran sesquiterpenes isolated from Crossopetalum tonduzii (1-8) and Maytenus macrocarpa (9) (Celastraceae) on the reversion of the resistant phenotype on a multidrug-resistant Leishmania line and their binding to recombinant C-terminal nucleotide-binding domain of Leishmania P-glycoprotein-like transporter were studied. The structures of the new compounds (1-5) were elucidated by spectroscopic methods, including (1)H-(13)C heteronuclear correlation (HMQC), long-range correlation spectra with inversal detection (HMBC), ROESY experiments, and chemical correlations. The absolute configuration of one of them (1) was determined by CD studies. The structure-activity relationship is discussed.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Daunorrubicina/farmacologia , Leishmania tropica/efeitos dos fármacos , Rosales/química , Sesquiterpenos/síntese química , Tripanossomicidas/síntese química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Dicroísmo Circular , Resistência a Múltiplos Medicamentos , Escherichia coli/metabolismo , Leishmania tropica/metabolismo , Ligação Proteica , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade , Tripanossomicidas/química , Tripanossomicidas/metabolismo , Tripanossomicidas/farmacologiaRESUMO
Five new sesquiterpenes (1-5) with a dihydro-beta-agarofuran skeleton were isolated from Crossopetalum tonduzii. Their structures were elucidated by means of 1H and 13C NMR spectroscopic studies, including homonuclear and heteronuclear correlation experiments (COSY, ROESY, HMQC, and HMBC). The absolute configurations of 1 and 2 were determined by CD studies and chemical correlation. Compounds 1-3 were assayed against Spodoptera littoralis in an election test and showed low insect-antifeedant activity.
