Withanolides from Aeroponically Grown Physalis peruviana and Their Selective Cytotoxicity to Prostate Cancer and Renal Carcinoma Cells.

Abstract

Investigation of aeroponically grown Physalis peruviana resulted in the isolation of 11 new withanolides, including perulactones I-L (1-4), 17-deoxy-23β-hydroxywithanolide E (5), 23β-hydroxywithanolide E (6), 4-deoxyphyperunolide A (7), 7β-hydroxywithanolide F (8), 7β-hydroxy-17-epi-withanolide K (9), 24,25-dihydro-23β,28-dihydroxywithanolide G (10), and 24,25-dihydrowithanolide E (11), together with 14 known withanolides (12-25). The structures of 1-11 were elucidated by the analysis of their spectroscopic data, and 12-25 were identified by comparison of their spectroscopic data with those reported. All withanolides were evaluated for their cytotoxic activity against a panel of tumor cell lines including LNCaP (androgen-sensitive human prostate adenocarcinoma), 22Rv1 (androgen-resistant human prostate adenocarcinoma), ACHN (human renal adenocarcinoma), M14 (human melanoma), SK-MEL-28 (human melanoma), and normal human foreskin fibroblast cells. Of these, the 17β-hydroxywithanolides (17-BHWs) 6, 8, 9, 11-13, 15, and 19-22 showed selective cytotoxic activity against the two prostate cancer cell lines LNCaP and 22Rv1, whereas 13 and 20 exhibited selective toxicity for the ACHN renal carcinoma cell line. These cytotoxicity data provide additional structure-activity relationship information for the 17-BHWs.

• Authors: Ya-Ming Xu, E M Kithsiri Wijeratne, Ashley L Babyak, Hanna R Marks, Alan D Brooks, Poonam Tewary, Li-Jiang Xuan, Wen-Qiong Wang, Thomas J Sayers, A A Leslie Gunatilaka
• Journal: Journal of natural products (J Nat Prod) Vol. 80 Issue 7 Pg. 1981-1991 (07 28 2017) ISSN: 1520-6025 [Electronic] United States
• PMID: 28617598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents, Phytogenic
• Withanolides

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Kidney Neoplasms (drug therapy)
• Male
• Melanoma (drug therapy)
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular
• Physalis (chemistry, growth & development)
• Prostatic Neoplasms (drug therapy)
• Structure-Activity Relationship
• Withanolides (chemistry, isolation & purification, pharmacology)