Antiproliferative and Anti-inflammatory Withanolides from Physalis angulata

Abstract

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.

Withanolides from the genus Physalis: a review on their phytochemical and pharmacological aspects

“…Physagulide P ( 61 ) was elucidated on the basis of extensive spectroscopic techniques . Withaperuvin E ( 62 ) has a special Δ 2 ‐1,4‐dione system in ring A. Physagulide O ( 71 ) and physangulatin I ( 72 ) are derived from P . angulata which possess 16β,17β‐epoxy groups.…”

“…Compounds 152 – 169 are intermediate withanolides with a 16‐ene group (Figure ). Physangulatins A‐H ( 159 – 166 ) were isolated from the stems and leaves of P. angulata , and their structures were established using extensive spectroscopic data analyses and X‐ray analysis . Moreover, physangulatin C ( 161 ) bears a β‐methyl group at C‐1′ and an α‐orientation 14,15‐acetal moiety.…”

“…Withaphysalin Y ( 299 ) as well as withaphysalin Z ( 304 ) were withaphysalins isolated from the stems and leaves of P . angulata …”

Actividad inmunoestimulante del extracto acuoso liofilizado de la planta entera de Physalis angulata L. en ratas albinas cepa Holtzman

“…Physalis angulata L "bolsa mullaca" es una especie de la familia Solanaceae, usada por nativos de la Amazonía peruana para el tratamiento de enfermedades respiratorias, problemas urinarios, artralgias y tumores (3) . Los frutos y otras partes aéreas han demostrado tener capacidades antiinflamatorias (4) , analgésicas (5) , antiparasitarias (6) , antimicrobianas (7) , antiespasmódicas (8) , y antimutagénicas (9,10) .…”

“…Se ha estudiado la posibilidad de que esta especie muestre efectos antiproliferativos por parte de las fisagulinas y witanólidos, en células tumorales humanas de cáncer de próstata, carcinoma renal y melanoma, asi como a efectos inhibitorios sobre la producción de óxido nítrico inducido por lipopolisacáridos en macrófagos (10) y antitumorales (tanto in vivo como in vitro); encontrándose efectos citotóxicos en varias líneas neoplásicas debido a la acción de algunas fisalinas provenientes del extracto acuoso liofilizado en concentraciones por encima de 6 µg/mL o de componentes aislados purificados de esta especie (IC 50 =0,58-15,18 µg/mL para fisalina B y 0,28-2,43 µg/ mL para fisalina D) (12,14) e inhibición de la proliferación tumoral como se observa por la reducción del patrón de tinción Ki67 en tumores de animales tratados (13) , de linfoma y de carcinoma de Erlich en modelos murinos (15) .…”