title: 5-Aminopyrazole-4-carboxamide analogues are selective inhibitors of Plasmodium falciparum microgametocyte exflagellation and potential malaria transmission blocking agents.
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.
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195, United States.
authors: Wenlin
authors: W
authors: Huang
authors: Division of Allergy & Infectious Disease, Center for Emerging & Reemerging Infectious Disease (CERID), University of Washington, Seattle, WA 98109, USA.
authors: Matthew A
authors: MA
authors: Hulverson
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195, United States.
authors: Zhongsheng
authors: Z
authors: Zhang
authors: Division of Allergy & Infectious Disease, Center for Emerging & Reemerging Infectious Disease (CERID), University of Washington, Seattle, WA 98109, USA.
authors: Ryan
authors: R
authors: Choi
authors: Department of Biochemistry and Molecular Biology, Center for Malaria Research, Pennsylvania State University, PA 16802, USA.
authors: Kevin J
authors: KJ
authors: Hart
authors: Department of Biochemistry and Molecular Biology, Center for Malaria Research, Pennsylvania State University, PA 16802, USA.
authors: Mark
authors: M
authors: Kennedy
authors: Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
authors: Rama Subba Rao
authors: RSR
authors: Vidadala
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195, United States; Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
authors: Dustin J
authors: DJ
authors: Maly
authors: Division of Allergy & Infectious Disease, Center for Emerging & Reemerging Infectious Disease (CERID), University of Washington, Seattle, WA 98109, USA. Electronic address: wesley@uw.edu.
authors: Wesley C
authors: WC
authors: Van Voorhis
authors: Department of Biochemistry and Molecular Biology, Center for Malaria Research, Pennsylvania State University, PA 16802, USA.
authors: Scott E
authors: SE
authors: Lindner
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195, United States. Electronic address: erkang@u.washington.edu.
authors: Erkang
authors: E
authors: Fan
authors: Division of Allergy & Infectious Disease, Center for Emerging & Reemerging Infectious Disease (CERID), University of Washington, Seattle, WA 98109, USA. Electronic address: ojo67kk@u.washington.edu.
authors: Kayode K
authors: KK
authors: Ojo
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D009033:Culicidae / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000517:prevention & control / Q000635:transmission; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases
chemical_list: D000962:Antimalarials; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D011720:Pyrazoles; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C000604556:5-aminopyrazole
keywords: 5-Aminopyrazole-4-carboxamide; Malaria transmission blocking; Microgametocyte exflagellation; PfCDPK4; Plasmodium falciparum