Isolation, structures, and structure - cytotoxic activity relationships of withanolides and physalins from Physalis angulata.
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.
Damu
Amooru G
AG
Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, Republic of China.
Kuo
Ping-Chung
PC
Su
Chung-Ren
CR
Kuo
Tsung-Hsiao
TH
Chen
Tzu-Hsuan
TH
Bastow
Kenneth F
KF
Lee
Kuo-Hsiung
KH
Wu
Tian-Shung
TS
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004875:Ergosterol / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007624:KB Cells; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D032321:Physalis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013624:Taiwan
D000972:Antineoplastic Agents, Phytogenic; D004875:Ergosterol