Details

Autor(en) / Beteiligte

• la Cruz, Artemisa Luévano-De
• Sanabria-Chanaga, Elkin Eduardo
• Yépez-Mulia, Lilián
• Castillo, Rafael
• Hernández-Campos, Alicia
• Nájera, Hugo
• Avitia-Domínguez, Claudia
• Sierra-Campos, Erick
• Valdez-Solana, Mónica
• Téllez-Valencia, Alfredo

Titel

Structural characterization, biochemical, inhibition and computational studies of Entamoeba histolytica phosphoglycerate mutase: finding hits for a new antiamoebic drug

Ist Teil von

• Medicinal chemistry research, 2018-06, Vol.27 (6), p.1705-1716

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Entamoeba histolytica is the causative agent of amoebiasis, which infects an estimated 50 million people globally each year. This parasite uses glycolysis as its only source of energy making enzymes of this route such as phosphoglycerate mutase (EhPGAM) excellent targets in the search for new drugs, a continuing necessity due to the adverse effects and unsuccessful cases of treatment that have resulted from the use of available antiparasitic agents. The aim of this work is to present the biochemical and structural characterization of EhPGAM and the results of a search for the first inhibitors of this enzyme. To this end, the activity of purified recombinant EhPGAM was assessed against an in-house chemical library of 200 benzimidazole derivatives. The results showed that seven compounds inhibited this enzyme about 40–70% at 100 μM and molecular dynamics simulations indicated that the two most potent inhibitors (Compound 1 and Compound 2 ) form stable complexes and have the highest binding energy. Hence, these inhibitors can be considered good candidates in the search of new drugs to treat amoebiasis.