Evaluation of the leishmanicidal and cytotoxic effects of inhibitors for microorganism metabolic pathway enzymes.

Abstract

Chemotherapy for leishmaniosis a neglected parasitic disease, is based on few drugs, which are toxic and present resistance issues. Efforts for the development of new therapies are essential for the control of leishmaniasis. Metabolic pathway enzymes are promising targets for new drugs against parasites. The search for effective drugs against key enzymes can take advantage of the similarities between metabolic pathways in different microorganisms trypanosomatids Trypanosoma cruzi and Leishmania and fungus Saccharomyces cerevisiae. In this report, leishmanicidal activity of the metabolic pathway enzymes inhibitors (IDs) of dihydroorotate dehydrogenase (DHODH), glyceraldehyde 3-phosphate dehydrogenase and cruzain-cysteine protease from T. cruzi and scitalona-desidratase, adenosine deaminase, succinate dehydrogenase complex II and hydroxynaphthalene reductase from S. cerevisiae was performed on Leishmania amazonensis extracellular promastigotes and amastigotes within macrophages. The most promising compound, ID195, which is a DHODH inhibitor was toxic against promastigotes and was selective for amastigotes over host cells.

DOI: 10.1016/j.biopha.2015.07.040

Cite this paper

@article{Barbosa2015EvaluationOT, title={Evaluation of the leishmanicidal and cytotoxic effects of inhibitors for microorganism metabolic pathway enzymes.}, author={Ademar de Mesquita Barbosa and Solange Dos Santos Costa and Josmar Rodrigues da Rocha and Carlos Alberto Montanari and Selma Giorgio}, journal={Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie}, year={2015}, volume={74}, pages={95-100} }