Interactions of antiparasitic sterols with sterol 14α-demethylase (CYP51) of human pathogens.
Sterol 14α-demethylase is a validated and an attractive drug target in human protozoan parasites. Pharmacological inactivation of this important enzyme has proven very effective against fungal infections, and it is a target that is being exploited for new antitrypanosomal and antileishmanial chemotherapy. We have used in silico calculations to identify previously reported antiparasitic sterol-like compounds and their structural congeners that have preferential and high docking affinity for CYP51. The sterol 14α-demethylase from Trypanosoma cruzi and Leishmania infantum, in particular, preferentially dock to taraxerol, epi-oleanolic acid, and α/β-amyrim structural scaffolds. These structural information and predicted interactions can be exploited for fragment/structure-based antiprotozoal drug design.
Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS 39217 USA.
Jasmine
J
Warfield
Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899 USA.
William N
WN
Setzer
Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS 39217 USA.
Ifedayo Victor
IV
Ogungbe
Antiparasitic; Docking; Protozoa; Sterol 14α-demethylase; Sterols