Active Compounds Against Anopheles minimus Carboxypeptidase B for Malaria Transmission-Blocking Strategy.
Malaria transmission-blocking compounds have been studied to block the transmission of malaria parasites, especially the drug-resistant Plasmodium. Carboxypeptidase B (CPB) in the midgut of Anopheline mosquitoes has been demonstrated to be essential for the sexual development of Plasmodium in the mosquito. Thus, the CPB is a potential target for blocking compounds. The aim of this research was to screen compounds from the National Cancer Institute (NCI) diversity dataset and U.S. Food and Drug Administration (FDA)-approved drugs that could reduce the Anopheles CPB activity. The cDNA fragment of cpb gene from An. minimus (cpbAmi) was amplified and sequenced. The three-dimensional structure of CPB was predicted from the deduced amino acid sequence. The virtual screening of the compounds from NCI diversity set IV and FDA-approved drugs was performed against CPBAmi. The inhibition activity against CPBAmi of the top-scoring molecules was characterized in vitro. Three compounds-NSC-1014, NSC-332670, and aminopterin with IC50 at 0.99 mM, 1.55 mM, and 0.062 mM, respectively-were found to significantly reduce the CPBAmi activity.
Department of Genetics, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand.
Watcharakorn
W
Mongkol
Department of Genetics, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand. Centre for Advanced Studies in Tropical Natural Resources, Kasetsart University, Bangkok, 10900, Thailand.
Uraiwan
U
Arunyawat
Department of Genetics, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand. Centre for Advanced Studies in Tropical Natural Resources, Kasetsart University, Bangkok, 10900, Thailand.
Wunrada
W
Surat
Department of Genetics, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand. Centre for Advanced Studies in Tropical Natural Resources, Kasetsart University, Bangkok, 10900, Thailand. fsciacs@ku.ac.th.
Anchanee
A
Kubera
D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000201:enzymology* / Q000235:genetics; D043424:Carboxypeptidase B / Q000037:antagonists & inhibitors* / Q000235:genetics; D003001:Cloning, Molecular; D008288:Malaria / Q000517:prevention & control* / Q000635:transmission; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D043424:Carboxypeptidase B
Anopheles minimus; Plasmodium; carboxypeptidase B; malaria; transmission-blocking