Phytochemical investigation of Physalis angulata was initiated following primary biological screening. Fractionation of CHCl3 and n-BuOH solubles of the MeOH extract from the whole plant was guided by in vitro cytotoxic activity assay using cultured HONE-1 and NUGC cells and led to the isolation of seven new withanolides, withangulatins B-H (1-7), and a new minor physalin, physalin W (8), along with 14 known compounds, including physaprun A, withaphysanolide, dihydrowithanolide E, physanolide A, withaphysalin A, and physalins B, D, F, G, I, J, T, U, and V. New compounds (1-8) were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS) and the relative stereochemical assignments based on NOESY correlations and analysis of coupling constants. Biological evaluation of these compounds against a panel of human cancer cell lines showed broad cytotoxic activity. Withangulatin B (1) and physalins D (10) and F (11) displayed potent cytotoxic activity against a panel of human cancer cell lines with EC50 values ranging from 0.2 to 1.6 microg/mL. Structure-activity relationship analysis indicated that withanolides and physalins with 4beta-hydroxy-2-en-1-one and 5beta,6beta-epoxy moieties are potential cytotoxic agents.
Three new sesquiterpene pyridine alkaloids, tripfordines A-C (1-3), were isolated from an ethanolic extract of the roots of Tripterygium wilfordii, along with eight known pyridine alkaloids, and tested for in vitro cytotoxic and anti-HIV activity. The structures of the new compounds were established on the basis of spectroscopic data interpretation. Anti-HIV structure-activity relationships (SAR) for this compound type are proposed on the basis of the screening results from the newly isolated compounds and prior data of known sesquiterpene pyridine alkaloids. The position of a carboxyalkyl chain on the pyridine moiety was not critical since both 2'- and 4'-substituted compounds exhibited high anti-HIV activity (EC(50) 0.1 microg/mL). In contrast, a hydroxy group at C-8' (carboxypropyl side chain) or C-9' (carboxybutyl side chain) was found to affect anti-HIV activity.
[reaction: see text] A novel withasteroid, physanolide A (1), with an unprecedented skeleton containing a seven-membered ring, and two new physalins, physalins U (2) and V (3), were isolated from Physalis angulata. The structures were elucidated from spectroscopic analysis, and plausible biosynthetic pathways were postulated. Physalins B (4), D (5), and F (6) showed strong cytotoxicity against multiple tumor cell lines, including KB, A431, HCT-8, PC-3, and ZR751, with EC(50) values less than 4 microg/mL.
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