Design and synthesis of Pfmrk inhibitors as potential antimalarial agents.
The synthesis and inhibitory activities of 10 potential inhibitors of Pfmrk, a Plasmodium falciparum cyclin-dependent protein kinase, are described. The most potent inhibitor is a 3-phenyl-quinolinone compound with an IC(50) value of 18 microM. It is the first compound reported to inhibit Pfmrk at the micro molar range.
Xiao
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Z
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Waters
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NC
Woodard
C L
CL
Li
Z
Z
Li
P K
PK
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry*; D018844:Cyclin-Dependent Kinases; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D000962:Antimalarials; D004791:Enzyme Inhibitors; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase