Development of Prolinol Containing Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: Rational Structure-Based Drug Design.

ABSTRACT: Inhibition of hypoxanthine-guanine-xanthine phosphoribosyltransferase activity decreases the pool of 6-oxo and 6-amino purine nucleoside monophosphates required for DNA and RNA synthesis, resulting in a reduction in cell growth. Therefore, inhibitors of this enzyme have potential to control infections, caused by Plasmodium falciparum and Plasmodium vivax, Trypanosoma brucei, Mycobacterium tuberculosis, and Helicobacter pylori. Five compounds synthesized here that contain a purine base covalently linked by a prolinol group to one or two phosphonate groups have K_i values ranging from 3 nM to >10 μM, depending on the structure of the inhibitor and the biological origin of the enzyme. X-ray crystal structures show that, on binding, these pro

SUBMITTER: Keough DT 

PROVIDER: S-EPMC11089518 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature