Abstract
Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) is essential for the exflagellation of male gametocytes. Inhibition of PfCDPK4 is an effective way of blocking the transmission of malaria by mosquitoes. A series of 5-aminopyrazole-4-carboxamide analogues are demonstrated to be potent inhibitors of PfCDPK4. The compounds are also able to block exflagellation of Plasmodium falciparum male gametocytes without observable toxicity to mammalian cells.
Keywords:
5-Aminopyrazole-4-carboxamide; Malaria transmission blocking; Microgametocyte exflagellation; PfCDPK4; Plasmodium falciparum.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antimalarials / chemistry*
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Antimalarials / pharmacology*
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Cell Line
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Culicidae / parasitology
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Humans
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Malaria, Falciparum / prevention & control
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Malaria, Falciparum / transmission
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Male
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Plasmodium falciparum / drug effects*
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Plasmodium falciparum / enzymology*
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Plasmodium falciparum / physiology
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology
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Protein Kinases / metabolism*
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Pyrazoles / chemistry*
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Pyrazoles / pharmacology*
Substances
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5-aminopyrazole
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Antimalarials
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Protein Kinase Inhibitors
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Pyrazoles
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Protein Kinases
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calcium-dependent protein kinase