title: Chemokine receptor CCR-5 inhibitors produced by Chaetomium globosum.
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.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA.
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Yang
authors.forename: Ronald
authors.initials: R
authors.lastname: Mierzwa
authors.forename: Joseph
authors.initials: J
authors.lastname: Terracciano
authors.forename: Mahesh
authors.initials: M
authors.lastname: Patel
authors.forename: Vincent
authors.initials: V
authors.lastname: Gullo
authors.forename: Nicole
authors.initials: N
authors.lastname: Wagner
authors.forename: Bahige
authors.initials: B
authors.lastname: Baroudy
authors.forename: Mohindar
authors.initials: M
authors.lastname: Puar
authors.forename: Tze-Ming
authors.initials: TM
authors.lastname: Chan
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McPhail
authors.forename: Min
authors.initials: M
authors.lastname: Chu
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001130:Arizona; D065100:CCR5 Receptor Antagonists; D002597:Chaetomium / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D006576:Heterocyclic Compounds, 4 or More Rings; C513451:Sch 210971; C513452:Sch 210972