1. Chemokine Receptor CCR-5 Inhibitors Produced byChaetomiumglobosum
- Author
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Mahesh J. Patel, † Tze-Ming Chan, Bahige Baroudy, Joseph Terracciano, Mohindar S. Puar, Min Chu, Nicole Wagner, Vincent P. Gullo, and Andrew T. McPhail, Ronald Mierzwa, and † Shu-Wei Yang
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Anti-HIV Agents ,Stereochemistry ,Pharmaceutical Science ,Chaetomium ,Pharmacognosy ,Crystallography, X-Ray ,Heterocyclic Compounds, 4 or More Rings ,Analytical Chemistry ,Inhibitory Concentration 50 ,Chemokine receptor ,Drug Discovery ,Humans ,Receptor ,IC50 ,Pharmacology ,Molecular Structure ,Chaetomium globosum ,Chemistry ,Organic Chemistry ,Arizona ,Biological activity ,In vitro ,Plant Leaves ,Complementary and alternative medicine ,Biochemistry ,CCR5 Receptor Antagonists ,Molecular Medicine ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Two novel chemokine receptor CCR-5 inhibitors, Sch 210971 (1) and Sch 210972 (2), were isolated from the fungal fermentation broth of Chaetomium globosum by normal- and reversed-phase HPLC purifications. The structure determination of 1 and 2 was accomplished on the basis of UV, MS, and NMR spectral data analyses including COSY, NOESY, HMQC, and HMBC experiments. The structure and relative configuration of 2 were determined unequivocally by X-ray crystallographic analysis. The major component 2 demonstrated a potent inhibitory activity of IC(50) = 79 nM in the CCR-5 receptor in vitro binding assay.
- Published
- 2006
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