Tenellones A and B from a Diaporthe sp.: two highly substituted benzophenone inhibitors of parasite cGMP-dependent protein kinase activity.
Parasite cGMP-dependent protein kinase (PKG) has been recently validated as a biochemical target for the treatment of coccidiosis. To discover new anticoccidial leads, we have screened our library of natural product extracts for inhibitors of parasite PKG. Bioassay-guided fractionation of the microbial extracts has led to the discovery of tenellones A (2) and B (3), two new highly substituted benzophenones. The isolation, structure, and activity of these compounds are described.
Zhang
Chaowei
C
Natural Products Chemistry and Human and Animal Infectious Disease, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
Ondeyka
John G
JG
Herath
Kithsiri B
KB
Guan
Ziqiang
Z
Collado
Javier
J
Platas
Gonzalo
G
Pelaez
Fernando
F
Leavitt
Penny S
PS
Gurnett
Anne
A
Nare
Bakela
B
Liberator
Paul
P
Singh
Sheo B
SB
D000818:Animals; D001577:Benzophenones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005658:Fungi / Q000737:chemistry*; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D013030:Spain; D014122:Toxoplasma / Q000378:metabolism
D001577:Benzophenones; D004791:Enzyme Inhibitors; C501148:tenellone A; C501149:tenellone B; D017869:Cyclic GMP-Dependent Protein Kinases