Highly substituted terphenyls as inhibitors of parasite cGMP-dependent protein kinase activity.
Parasite cGMP-dependent protein kinase (PKG) is one of the validated biochemical targets for the treatment of coccidiosis. We screened our library of natural product extracts for inhibitors of parasite PKG for the discovery of anticoccidial leads. Terferol (1) and three new terphenyls (2, 3, and 4) were isolated using bioassay-guided fractionation of the microbial extract of a Phoma sp. by a high-throughput two-step isolation method employing LH-20 and reversed-phase HPLC. These compounds inhibited parasite PKG with IC(50) values in the range 0.9-5.8 microM.
Zhang
Chaowei
C
Natural Products Chemistry and Human and Animal Infectious Disease, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA.
Ondeyka
John G
JG
Herath
Kithsiri B
KB
Guan
Ziqiang
Z
Collado
Javier
J
Pelaez
Fernando
F
Leavitt
Penny S
PS
Gurnett
Anne
A
Nare
Bakela
B
Liberator
Paul
P
Singh
Sheo B
SB
D000818:Animals; D001203:Ascomycota / Q000737:chemistry*; D003048:Coccidiosis / Q000188:drug therapy*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D016786:Eimeria tenella / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005602:France; D015394:Molecular Structure; D013730:Terphenyl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013730:Terphenyl Compounds; C040546:terferol; D017869:Cyclic GMP-Dependent Protein Kinases