title: 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: Department of Pharmaceutical Sciences, College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii 96720, USA.
authors: Ihsan-ul-Haq
authors: Ui Joung
authors: UJ
authors: Youn
authors: Xingyun
authors: X
authors: Chai
authors: Eun-Jung
authors: EJ
authors: Park
authors: Tamara P
authors: TP
authors: Kondratyuk
authors: Charles J
authors: CJ
authors: Simmons
authors: Robert P
authors: RP
authors: Borris
authors: Bushra
authors: B
authors: Mirza
authors: John M
authors: JM
authors: Pezzuto
authors: Leng Chee
authors: LC
authors: Chang
mesh_terms: D000818:Animals; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D019906:Nuclear Magnetic Resonance, Biomolecular; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D032341:Withania / Q000737:chemistry*; D054358:Withanolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D054358:Withanolides; D009569:Nitric Oxide