title: Highly substituted terphenyls as inhibitors of parasite cGMP-dependent protein kinase activity.
abstract: 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.
authors.affiliation: Natural Products Chemistry and Human and Animal Infectious Disease, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA.
authors.forename: Chaowei
authors.initials: C
authors.lastname: Zhang
authors.forename: John G
authors.initials: JG
authors.lastname: Ondeyka
authors.forename: Kithsiri B
authors.initials: KB
authors.lastname: Herath
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Guan
authors.forename: Javier
authors.initials: J
authors.lastname: Collado
authors.forename: Fernando
authors.initials: F
authors.lastname: Pelaez
authors.forename: Penny S
authors.initials: PS
authors.lastname: Leavitt
authors.forename: Anne
authors.initials: A
authors.lastname: Gurnett
authors.forename: Bakela
authors.initials: B
authors.lastname: Nare
authors.forename: Paul
authors.initials: P
authors.lastname: Liberator
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D013730:Terphenyl Compounds; C040546:terferol; D017869:Cyclic GMP-Dependent Protein Kinases