5-Aminopyrazole-4-carboxamide analogues are selective inhibitors of Plasmodium falciparum microgametocyte exflagellation and potential malaria transmission blocking agents

[Display omitted] 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 demon...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2016-11, Vol.26 (22), p.5487-5491
Main Authors: Huang, Wenlin, Hulverson, Matthew A., Zhang, Zhongsheng, Choi, Ryan, Hart, Kevin J., Kennedy, Mark, Vidadala, Rama Subba Rao, Maly, Dustin J., Van Voorhis, Wesley C., Lindner, Scott E., Fan, Erkang, Ojo, Kayode K.
Format: Article
Language:English
Subjects:
5-Aminopyrazole-4-carboxamide
Animals
Antimalarials - chemistry
Antimalarials - pharmacology
Cell Line
Culicidae - parasitology
Humans
Malaria transmission blocking
Malaria, Falciparum - prevention & control
Malaria, Falciparum - transmission
Male
Microgametocyte exflagellation
PfCDPK4
Plasmodium falciparum
Plasmodium falciparum - drug effects
Plasmodium falciparum - enzymology
Plasmodium falciparum - physiology
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - pharmacology
Protein Kinases - metabolism
Pyrazoles - chemistry
Pyrazoles - pharmacology
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Summary:[Display omitted] 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2016.10.014