RESUMO
Sixteen new withanolides, physangulatins A-N (1-14) and withaphysalins Y and Z (15 and 16), as well as 12 known analogues, were isolated from the stems and leaves of Physalis angulata L. Their structures were established using extensive spectroscopic data analyses. The absolute configurations of 1 and 9 were assigned via X-ray crystallography. The isolated compounds were tested for their antiproliferative effects against human prostate cancer cells (C4-2B and 22Rvl), human renal carcinoma cells (786-O, A-498, and ACHN), and human melanoma cells (A375-S2), as well as inhibitory effects on NO production induced by LPS in macrophages. Compounds 9, 17, 20, 21, 25, and 27 showed antiproliferative effects against all tested cancer cells, with IC50 values of 0.18-7.43 µM. Compounds 3-5, 9-11, 17, 20-22, 24, 25, and 27 displayed inhibitory effects against NO production, with IC50 values of 1.36-11.59 µM.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Physalis/química , Vitanolídeos/isolamento & purificação , Vitanolídeos/farmacologia , Anti-Inflamatórios/química , Antineoplásicos Fitogênicos/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Humanos , Concentração Inibidora 50 , Neoplasias Renais/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Conformação Molecular , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Caules de Planta/química , Neoplasias da Próstata/tratamento farmacológico , Vitanolídeos/químicaRESUMO
Five new physalins, including a novel 1,10-seco one, physalin V (1), a tricarboxylic acid cycle one, physalin VIII (5), a rare 11,15-cyclo one, physalin IX (6), and two new ones, physalins VI (2) and VII (4) were isolated from stems and leaves of Physalis angulata together with eleven known analogues (3 and 7-16). Their structures were established by MS, IR, UV, and NMR spectroscopic analysis, together with the X-ray diffraction analysis of neophysalin, physalin P (12), and the structure of physalin D1 (3) has been revised here. These isolated compounds were evaluated for their antiproliferative activities against human cancer cells (C4-2B, 22Rv1, 786-O, A-498, ACHN, and A375-S2) and inhibitory effects on nitric oxide production. Compounds 9 and 10 showed antiproliferative activities against all tested human cancer cells with IC50 values of 0.24-3.17 µM. Compounds 1, 3, 4, 9, 10, 13, 14, and 16 exhibited inhibitory activities against NO production. The IC50 values of compounds 9, 10, 13, and 16 were between 0.32 and 4.03 µM, while compounds 1, 3, 4, and 14 had IC50 values of 12.83-34.19 µM. Herein, plausible biosynthetic pathways for rare structures 1 and 6 and structure-activity relationships on the inhibition of NO production for all isolated compounds are discussed.