Physalins V-IX 1624-cyclo-1314-seco withanolides from Physalis angulata and their antiproliferative and anti-inflammatory activities

摘要

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.