Discovery of isoxazolyl-based inhibitors of Plasmodium falciparum cGMP-dependent protein kinase.

Shams Ul MahmoodHuimin ChengSreedhar R TummalapalliRamappa ChakrasaliRammohan R Yadav BheemanaboinaTamara KreissAgnieska ChojnowskiTyler EckJohn J SiekierkaDavid P Rotella

Published in: RSC medicinal chemistry (2019)

The cGMP-dependent protein kinase in Plasmodium falciparum (PfPKG) plays multiple roles in the life cycle of the parasite. As a result, this enzyme is a potential target for new antimalarial agents. Existing inhbitors, while potent and active in malaria models are not optimal. This communication describes initial optimization of a structurally distinct class of PfPKG inhibitors.

Keyphrases

plasmodium falciparum
protein kinase
life cycle
small molecule
nitric oxide
high throughput
climate change
risk assessment