Cyclin-dependent kinase inhibitors block erythrocyte invasion and intraerythrocytic development of Babesia bovis in vitro.
SUMMARYCyclin-dependent kinases (CDKs) are essential for the regulation of the eukaryotic cell cycle. A number of chemicals, which selectively inhibit the CDK activities, have been synthesized for the development of anti-cancer drugs. This report describes the inhibitory effect of purine derivatives known to be CDK inhibitors on the asexual growth of Babesia bovis. The 4 compounds, roscovitine, purvalanol A, CGP74514A, and CDK2 Inhibitor II, showed significantly suppressive effects on the in vitro growth of B. bovis. Three (roscovitine, purvalanol A, and CDK2 Inhibitor II) showed an inhibitory effect on the early stages of intraerythrocytic development of B. bovis. CGP74514A (CDK1-specific inhibitor) blocked the erythrocyte invasion by merozoites. Our data suggest the chemotherapeutic potential of the CDK inhibitors for babesiosis, and the target molecules of the compounds would participate in the process of successful erythrocyte invasion or intraerythrocytic development of B. bovis.
Nakamura
K
K
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
Yokoyama
N
N
Igarashi
I
I
D000818:Animals; D016793:Babesia bovis / Q000187:drug effects* / Q000254:growth & development; D001404:Babesiosis / Q000517:prevention & control*; D002417:Cattle; D002418:Cattle Diseases / Q000469:parasitology* / Q000517:prevention & control*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004912:Erythrocytes / Q000469:parasitology*; D052940:Merozoites / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013997:Time Factors
D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases