Physalins V-IX, 16,24-cyclo-13,14-seco withanolides from Physalis angulata and their antiproliferative and anti-inflammatory activities

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 D(1) (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 IC(50) values of 0.24–3.17 μM. Compounds 1, 3, 4, 9, 10, 13, 14, and 16 exhibited inhibitory activities against NO production. The IC(50) values of compounds 9, 10, 13, and 16 were between 0.32 and 4.03 μM, while compounds 1, 3, 4, and 14 had IC(50) 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.