Structure-based inhibitor screening: a family of sulfonated dye inhibitors for malaria parasite triosephosphate isomerase.

The crystal structure of malaria triosephosphate isomerase (TIM) was screened against the National Cancer Institute database of three-dimensional molecular structures. Ten top-scoring commercially available compounds were analyzed for inhibition of recombinant TIM. Two anionic dyes showed inhibition of TIM at concentrations of <100 mM. Four related sulfonated dyes were identified from the literature, docked, and screened in vitro. All showed inhibition of malaria TIM. Models indicate that these compounds bind in two suggested conformations to the active site region of the TIM enzyme. These compounds may be used in rational modification procedures for the synthesis of lead anti-TIM drugs.