Molecules, Vol. 24, Pages 3216: Leishmania mexicana Trypanothione Reductase Inhibitors: Computational and Biological Studies

Molecules, Vol. 24, Pages 3216: Leishmania mexicana Trypanothione Reductase Inhibitors: Computational and Biological Studies Molecules doi: 10.3390/molecules24183216 Authors: Félix Matadamas-Martínez Alicia Hernández-Campos Alfredo Téllez-Valencia Alejandra Vázquez-Raygoza Sandra Comparán-Alarcón Lilián Yépez-Mulia Rafael Castillo Leishmanicidal drugs have many side effects, and drug resistance to all of them has been documented. Therefore, the development of new drugs and the identification of novel therapeutic targets are urgently needed. Leishmania mexicana trypanothione reductase (LmTR), a NADPH-dependent flavoprotein oxidoreductase important to thiol metabolism, is essential for parasite viability. Its absence in the mammalian host makes this enzyme an attractive target for the development of new anti-Leishmania drugs. Herein, a tridimensional model of LmTR was constructed and the molecular docking of 20 molecules from a ZINC database was performed. Five compounds (ZINC04684558, ZINC09642432, ZINC12151998, ZINC14970552, and ZINC11841871) were selected (docking scores −10.27 kcal/mol to −5.29 kcal/mol and structurally different) and evaluated against recombinant LmTR (rLmTR) and L. mexicana promastigote. Additionally, molecular dynamics simulation of LmTR-selected compound complexes was achieved. The five selected compounds inhibited rLmTR activity in the range of 32.9% to 40.1%. The binding of selected compounds to...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research