Chemokine receptor CCR-5 inhibitors produced by Chaetomium globosum.
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.
Yang
Shu-Wei
SW
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA.
Mierzwa
Ronald
R
Terracciano
Joseph
J
Patel
Mahesh
M
Gullo
Vincent
V
Wagner
Nicole
N
Baroudy
Bahige
B
Puar
Mohindar
M
Chan
Tze-Ming
TM
McPhail
Andrew T
AT
Chu
Min
M
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
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D006576:Heterocyclic Compounds, 4 or More Rings; C513451:Sch 210971; C513452:Sch 210972