Isolation and structure elucidation of Sch 642305, a novel bacterial DNA primase inhibitor produced by Penicillium verrucosum.
A novel primase inhibitor, Sch 642305 (1), was isolated from the fermentation broth of the fungal culture Penicillium verrucosum. The structure of 1 was elucidated on the basis of MS and NMR spectroscopic data as a new and unusual bicyclic 10-membered macrolide. The absolute configuration of the asymmetric centers was determined by X-ray crystallographic analysis of the p-bromobenzoate derivative (3). Compound 1 exhibited inhibitory activity against bacterial DNA primase enzyme with an EC(50) of 70 microM.
Chu
Min
M
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. min.chu@spcorp.com
Mierzwa
Ronald
R
Xu
Ling
L
He
Ling
L
Terracciano
Joseph
J
Patel
Mahesh
M
Gullo
Vincent
V
Black
Todd
T
Zhao
Wenjun
W
Chan
Tze-Ming
TM
McPhail
Andrew T
AT
D001130:Arizona; D018360:Crystallography, X-Ray; D019915:DNA Primase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005285:Fermentation; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010407:Penicillium / Q000737:chemistry*
D004791:Enzyme Inhibitors; D018942:Macrolides; C482741:Sch 642305; D019915:DNA Primase