John A Gilleran, Kutub Ashraf, Melvin Delvillar, Tyler Eck, Raheel Fondekar, Edward B Miller, Ashley Hutchinson, Aiping Dong, Alma Seitova, Mariana Laureano De Souza, David Augeri, Levon Halabelian, John Siekierka, David P Rotella, John Gordon, Wayne E Childers, Mark C Grier, Bart L Staker, Jacques Y Roberge, Purnima Bhanot
Controlling malaria requires new drugs against Plasmodium falciparum . The P. falciparum cGMP-dependent protein kinase (PfPKG) is a validated target whose inhibitors could block multiple steps of the parasite's life cycle. We defined the structure-activity relationship (SAR) of a pyrrole series for PfPKG inhibition. Key pharmacophores were modified to enable full exploration of chemical diversity and to gain knowledge about an ideal core scaffold. In vitro potency against recombinant PfPKG and human PKG were used to determine compound selectivity for the parasite enzyme...
February 19, 2024: Journal of Medicinal Chemistry