Genetic resistance to purine nucleoside phosphorylase inhibition in Plasmodium falciparum.

ABSTRACT: Plasmodium falciparum causes the most lethal form of human malaria and is a global health concern. The parasite responds to antimalarial therapies by developing drug resistance. The continuous development of new antimalarials with novel mechanisms of action is a priority for drug combination therapies. The use of transition-state analog inhibitors to block essential steps in purine salvage has been proposed as a new antimalarial approach. Mutations that reduce transition-state analog binding are also expected to reduce the essential catalytic function of the target. We have previously reported that inhibition of host and P. falciparum purine nucleoside phosphorylase (PfPNP) by DADMe-Immucillin-G (DADMe-ImmG) causes purine starvation and parasite death in vitro and in p

SUBMITTER: Ducati RG 

PROVIDER: S-EPMC5834662 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature