Identification and characterization of thiamine analogs with antiplasmodial activity.

ABSTRACT: Thiamine is metabolized into thiamine pyrophosphate (TPP), an essential enzyme cofactor. Previous work has shown that oxythiamine, a thiamine analog, is metabolized by thiamine pyrophosphokinase (TPK) into oxythiamine pyrophosphate within the malaria parasite Plasmodium falciparum and then inhibits TPP-dependent enzymes, killing the parasite in vitro and in vivo. To identify a more potent antiplasmodial thiamine analog, 11 commercially available compounds were tested against P. falciparum and P. knowlesi. Five active compounds were identified, but only N3-pyridyl thiamine (N3PT), a potent transketolase inhibitor and candidate anticancer lead compound, was found to suppress P. falciparum proliferation with an IC₅₀ value 10-fold lower than

SUBMITTER: Fathoni I 

PROVIDER: S-EPMC11619390 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature