RESUMO
In this paper is described a synthetic route to 6ß-phenylamino-cholestan-3ß,5α-diol and (25R)-6ß-phenylaminospirostan-3ß,5α-diol, starting from cholesterol and diosgenin, respectively. The products were obtained in two steps by epoxidation followed by aminolysis, through an environmentally friendly and solvent-free method mediated by SZ (sulfated zirconia) as catalyst. The use of SZ allows chemo- and regioselective ring opening of the 5,6α-epoxide during the aminolysis reaction eliminating the required separation of the epoxide mixture. The products obtained were spectroscopically characterized by 1H, PENDANT 13C NMR and HETCOR experiments, and complemented with FTIR-ATR and HRMS. The antiproliferative effect of the ß-aminoalcohols was evaluated on MCF-7 cells after 48h of incubation, by MTT and CVS assays. These methodologies showed that both compounds have antiproliferative activity, being more active the cholesterol analogue. Additionally, the cell images obtained by Harris' Hematoxylin and Eosin (H&E) staining protocol, evidenced formation of apoptotic bodies due to the presence of the obtained ß-aminoalcohols in a dose-dependent manner.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Colestanóis/síntese química , Colestanóis/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Colestanóis/química , Humanos , Células MCF-7RESUMO
Certain steroidal compounds have demonstrated an antiproliferative effect against several tumor cell lines; however, their complete role on cancer cells is not currently established. Herein, we report the synthesis and evaluation of two new 26-hydroxy-22-oxocholestanic steroids on cervical cancer CaSki cells. The title compounds were prepared from diosgenin and hecogenin in excellent yields. We determined their effect on cell proliferation, cell cycle, and cell death. The cytotoxic effect of the title compounds on CaSki and human lymphocytes was also evaluated, indicating that the main cell death process is not necrosis; the null effect on lymphocytes implies that they are not cytotoxic. The observation of apoptotic bodies as well as the increase in the expression of active caspase-3 along with the fragmentation of DNA confirmed that such new cholestanic frameworks induced apoptosis in tumor cells. Significantly, their antiproliferative activity on tumor cells did not affect the proliferative potential of normal fibroblasts from cervix and peripheral blood lymphocytes. The title compounds show selective antitumor activity and therefore serve as promising lead candidates for further optimization.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Colestanóis/química , Colestanóis/síntese química , Colestanóis/farmacologia , Diosgenina/química , Sapogeninas/química , Esteroides/química , Esteroides/síntese química , Esteroides/farmacologia , Sequência de Carboidratos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Corantes Fluorescentes , Humanos , Marcação In Situ das Extremidades Cortadas , Indóis , Linfócitos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Relação Estrutura-Atividade , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologiaRESUMO
In this paper we report the synthesis of four fluorinated analogues of brassinosteroids in which fluorine was introduced stereoselectively at C-2. The bioactivity of these new compounds was evaluated using the rice lamina inclination test. The results show that two of these analogues elicit high bioactivity, suggesting the involvement of hydrogen bond interactions between the active brassinosteroids and their cellular receptor.
Assuntos
Colestanóis/síntese química , Colestanóis/farmacologia , Halogenação/efeitos dos fármacos , Esteroides Heterocíclicos/síntese química , Esteroides Heterocíclicos/farmacologia , Bioensaio , Brassinosteroides , Colestanóis/química , Oryza/efeitos dos fármacos , Esteroides Heterocíclicos/químicaRESUMO
Five new steroid sulfates, sodium 2beta,3alpha-dihydroxy-5alpha-cholestane 3-sulfate (6), sodium 2beta,3alpha-dihydroxy-5alpha-cholestane 2-sulfate (7), disodium 2beta,3alpha-dihydroxy-5alpha-cholestane disulfate (8), sodium 3alpha-acetoxy-2beta-hydroxy-5alpha-cholestane 2-sulfate (12), and sodium 2beta-acetoxy-3alpha-hydroxy-5alpha-cholestane 3-sulfate (13), have been synthesized starting from 3beta-hydroxy-5alpha-cholestane (1). The synthetic steroids were completely characterized by one-dimensional and two-dimensional NMR and FABMS spectra. Sulfation was performed using triethylamine-sulfur trioxide complex in dimethylformamide as the sulfating agent. The sulfated steroids were comparatively evaluated for their inhibitory effect on the replication of herpes simplex virus type 2 (HSV-2). Compounds 7 and 8 were the most effective in their inhibitory action against HSV-2. The disulfated steroid 8 also proved to be active against DEN-2 and JV.