Structural characterization, biochemical, inhibition and computational studies of Entamoeba histolytica phosphoglycerate mutase: finding hits for a new antiamoebic drug
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.
KeywordsAmoebiasis Phosphoglycerate mutase Enzyme inhibition Homology modeling Molecular dynamics Benzimidazole derivatives
The authors acknowledge DGESCA for the use of supercomputer Miztli. ATV and CAD acknowledge CONACyT for grants No. 257848 and No. 258694, respectively. CONACyT is also acknowledged by ALC (fellowship No. 231153) and EESC (fellowship No. 283595).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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