title: Inhibition of the human chemokine receptor CCR5 by variecolin and variecolol and isolation of four new variecolin analogues, emericolins A-D, from Emericella aurantiobrunnea.
abstract: An extract from the fungus Emericella aurantiobrunnea was found to compete with macrophage inflammatory protein (MIP)-1alpha for binding to human CCR5 in a scintillation proximity assay (SPA). Bioassay-guided fractionation led to the isolation of variecolin (1) and variecolol (2), which had IC50 values of 9 and 32 microM, respectively. An X-ray crystal structure of variecolin (1) was obtained for the first time. Also isolated were four new inactive analogues, emericolin A (3), B (4), C (5), and D (6), and the relative stereochemistry of these compounds was determined by NMR methods using ROESY spectra and 1H/1H coupling constants.
authors.affiliation: MerLion Pharmaceuticals, 1 Science Park Road, The Capricorn #05-01, Singapore Science Park II, 117528.
authors.forename: K
authors.initials: K
authors.lastname: Yoganathan
authors.forename: Christine
authors.initials: C
authors.lastname: Rossant
authors.forename: Robert P
authors.initials: RP
authors.lastname: Glover
authors.forename: Shugeng
authors.initials: S
authors.lastname: Cao
authors.forename: Jagadese J
authors.initials: JJ
authors.lastname: Vittal
authors.forename: Siewbee
authors.initials: S
authors.lastname: Ng
authors.forename: Yicun
authors.initials: Y
authors.lastname: Huang
authors.forename: Antony D
authors.initials: AD
authors.lastname: Buss
authors.forename: Mark S
authors.initials: MS
authors.lastname: Butler
mesh_terms: D001203:Ascomycota / Q000737:chemistry*; D065100:CCR5 Receptor Antagonists; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018360:Crystallography, X-Ray; D006801:Humans; D020128:Inhibitory Concentration 50; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D065100:CCR5 Receptor Antagonists; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D013729:Terpenes; C433945:variecolin; C493694:variecolol