RESUMO
Two new cassaine-type diterpenoids, namely erythrofordins D (1) and E (2), sourced from a Cameroon collection of Erythrophleum suaveolens were isolated and assessed for anti-tumor activity. In the NCI-60 cancer cell assay, erythrofordins D (1) and E (2) were found to be cytotoxic in the low micro molar ranges with a mean GI50 value of 2.45 and 0.71⯵M, mean TGI value of 9.77 and 2.29⯵M, and a mean LC50 of 26.92 and 11.48⯵M for 1 and 2 respectively. Using the COMPARE algorithm, the new compounds were found to have similar NCI-60 response profiles to the known cardiac glycosides hyrcanoside and strophanthin. In addition, in an assay examining the viability and contractile function in human cardiomyocytes derived from induced pluripotent stem-cells, erythrofordins showed cardiotoxicity effects at concentrations as low as 0.03⯵g/mL.
Assuntos
Caesalpinia/química , Diterpenos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Demand for the experimental antineoplastic agent schweinfurthin A, for developmental testing, prompted a re-collection of leaf material of Macaranga schweinfurthii from the original collection site in Cameroon. During chromatographic purification of the organic solvent extract, analytical UPLC-PDA-TOFMS of stilbene-enriched fractions revealed the presence of six known schweinfurthins and two previously unknown stilbenes. The structures of these new compounds, schweinfurthins I and J (1 and 2), were elucidated by 1D- and 2D-NMR techniques.
