Active Compounds Against Anopheles minimus Carboxypeptidase B for Malaria Transmission-Blocking Strategy

作者：Mongkol Watcharakorn; Arunyawat Uraiwan; Surat Wunrada; Kubera Anchanee^*

来源：Journal of Medical Entomology, 2015, 52(6): 1322-1332.

DOI：10.1093/jme/tjv133

• malaria
• transmission-blocking
• Plasmodium
• Anopheles minimus
• carboxypeptidase B

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.

• 出版日期2015-11