RESUMO
A new dimeric withanolide, ashwagandhanolide (1), was isolated from the roots of an Ayurvedic medicinal herb, Withania somnifera. A detailed spectroscopic evaluation revealed its identity as a dimer with an unusual thioether linkage. Compound 1 displayed growth inhibition against human gastric (AGS), breast (MCF-7), central nervous system (SF-268), colon (HCT-116), and lung (NCI H460) cancer cell lines, with IC50 values in the range 0.43-1.48 microg/mL. In addition, it inhibited lipid peroxidation and the activity of the enzyme cyclooxygenase-2 in vitro.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Inibidores de Ciclo-Oxigenase/isolamento & purificação , Ergosterol/análogos & derivados , Plantas Medicinais/química , Withania/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Ergosterol/química , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Humanos , Índia , Peroxidação de Lipídeos/efeitos dos fármacos , Estrutura Molecular , Raízes de Plantas/químicaRESUMO
The antioxidant ferulic and caffeic acid phenolics are ubiquitous in plants and abundant in fruits and vegetables. We have synthesized a series of ferulic and caffeic acid esters and tested for tumor cell proliferation, cyclooxygenase enzymes (COX-1 and -2) and lipid peroxidation inhibitory activities in vitro. In the tumor cell proliferation assay, some of these esters showed excellent growth inhibition of colon cancer cells. Among the phenolics esters assayed, compounds 10 (C12-caffeate), 11 (C16-caffeate), 21 (C8-ferulate), and 23 (C12-ferulate) showed strong growth inhibition with IC50 values of 16.55, 13.46, 18.67, and 7.57 microg/mL in a breast cancer cell line; 9.65, 7.45, 17.05, and 4.35 microg/ mL in a lung cancer cell line; 5.78, 3.5, 4.29, and 2.46 microg/mL in a colon cancer cell line; 12.04, 12.21, 14.63, and 8.09 microg/ mL in a central nervous system cancer cell line; and 8.62, 7.76, 11.0, and 5.37 in a gastric cancer cell line. In COX enzyme inhibitory assays, ferulic and caffeic acid esters significantly inhibited both COX-1 and COX-2 enzymes. Caffeates 5-10 (C4-C12), inhibited COX-1 enzyme between 50% and 90% and COX-2 enzyme by about 70%, whereas ferulates 15-21 (C3-C8) inhibited COX-1 and COX-2 enzymes by 85-95% 25 microg/mL. Long-chain caffeates 11-14 (C16-C22) and short-chain ferulates 15-20 (C3-C5) were the most active in lipid peroxidation inhibition and showed 60-70% activity at 5 microg/mL concentration.
Assuntos
Ácidos Cafeicos/farmacologia , Divisão Celular/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Ésteres/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias/patologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Ácidos Cafeicos/síntese química , Linhagem Celular Tumoral , Ácidos Cumáricos/química , Inibidores de Ciclo-Oxigenase/farmacologia , Ésteres/síntese química , Humanos , Espectroscopia de Ressonância Magnética , Neoplasias/enzimologia , Neoplasias/metabolismoRESUMO
Two triterpenoid glycosides have been isolated along with 10 known saponins from Bacopa monnieri. Structures of the compounds have been elucidated as 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] jujubogenin (1) and 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] pseudojujubogenin (2) by high resolution NMR spectral data and chemical correlations. Further, the chemical compositions of bacosides A and B have been delineated.