Isolation, Structures, and Structure−Cytotoxic Activity Relationships of Withanolides and Physalins from Physalis angulata

• Published in: Journal of natural products (Washington, D.C.) Vol. 70; no. 7; pp. 1146 - 1152
• Main Authors: Damu, Amooru G, Kuo, Ping-Chung, Su, Chung-Ren, Kuo, Tsung-Hsiao, Chen, Tzu-Hsuan, Bastow, Kenneth F, Lee, Kuo-Hsiung, Wu, Tian-Shung
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.07.2007; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Biological and medical sciences; Chemistry, Medicinal; Drug Screening Assays, Antitumor; Ergosterol - analogs & derivatives; Ergosterol - chemistry; Ergosterol - isolation & purification; Ergosterol - pharmacology; General pharmacology; Humans; KB Cells; Life Sciences & Biomedicine; Medical sciences; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physalis - chemistry; Plant Sciences; Science & Technology; Structure-Activity Relationship; Taiwan; Taiwan; QUINONE REDUCTASE; SOLANACEAE; ERGOSTANE-TYPE STEROIDS; PERUVIANA; OCCURRING STEROIDAL LACTONES; 17ALPHA-ORIENTED SIDE-CHAIN; INDUCTION; PHILADELPHICA; CONSTITUENTS; WITHAPERUVIN; Steroid; Relative configuration; Overhauser effect; Cytotoxicity; Extract; Nasopharynx; NMR spectrometry; Medicinal plant; Acetal; Structure activity relation; Dicotyledones; Angiospermae; Solanaceae; Tumor cell; Human; Stomach; Pharmacognosy; Physalis; Whole plant; Polycyclic compound; Lactone; In vitro; Two dimension spectrometry; Screening; Cell line; Epoxide; Plant origin; Isolation; Spermatophyta; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np0701374

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 μg/mL. Structure−activity relationship analysis indicated that withanolides and physalins with 4β-hydroxy-2-en-1-one and 5β,6β-epoxy moieties are potential cytotoxic agents.