Biologically active withanolides from Withania coagulans.

Abstract

Bioassay-directed isolation and purification of the crude extract of Withania coagulans, using two assays for cancer chemopreventive mechanisms, led to the isolation of three new steroidal lactones, withacoagulin G (1), withacoagulin H (2), and withacoagulin I (3), along with six known derivatives (4-9). The structures and absolute stereochemistry of these compounds were determined on the basis of spectroscopic analyses, including 1D and 2D NMR, mass spectrometry, and CD analyses. The structure of 1 was confirmed using X-ray diffraction methods. Compounds 1-9 inhibited nitric oxide production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells with IC(50) values in the range of 1.9-38.2 μM. Compounds 1 and 2 were the most active (IC(50) 3.1 and 1.9 μM, respectively). Withanolides 1-9 exhibited inhibition of tumor necrosis factor-α (TNF-α)-induced nuclear factor-kappa B (NF-κB) activation with IC(50) values in the range of 1.60-12.4 μM.

• Authors: Ihsan-ul-Haq, Ui Joung Youn, Xingyun Chai, Eun-Jung Park, Tamara P Kondratyuk, Charles J Simmons, Robert P Borris, Bushra Mirza, John M Pezzuto, Leng Chee Chang
• Journal: Journal of natural products (J Nat Prod) Vol. 76 Issue 1 Pg. 22-8 (Jan 25 2013) ISSN: 1520-6025 [Electronic] United States
• PMID: 23316950 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Withanolides
• Nitric Oxide

Topics

• Animals
• Lipopolysaccharides (pharmacology)
• Macrophages (drug effects)
• Mice
• Molecular Structure
• NF-kappa B (drug effects)
• Nitric Oxide (biosynthesis)
• Nuclear Magnetic Resonance, Biomolecular
• Tumor Necrosis Factor-alpha (drug effects)
• Withania (chemistry)
• Withanolides (chemistry, isolation & purification, pharmacology)
• X-Ray Diffraction