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RESEARCH PRODUCT
Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates
Santiago RodríguezMarcel KaiserMarcel KaiserFlorenci V. GonzálezSantiago RoyoTanja SchirmeisterSascha JungJosé M. Bautistasubject
0301 basic medicinesleeping sicknessClinical BiochemistryPharmaceutical Science01 natural sciencesBiochemistryCathepsin BinhibitorsDrug Discoverychemistry.chemical_classificationbiologyChemistryDipeptidesHep G2 CellsMolecular Docking SimulationCysteine EndopeptidasesBiochemistryAntiprotozoalMolecular MedicineChagas diseaseProteasesCell Survivalmedicine.drug_classPlasmodium falciparumTrypanosoma brucei bruceimalariaAntiprotozoal AgentsCysteine Proteinase InhibitorsTrypanosoma bruceicysteine proteasesInhibitory Concentration 50Structure-Activity Relationship03 medical and health sciencesparasitic diseasesmedicineHumansTrypanosoma cruziMolecular Biologychagas diseaseBinding Sites010405 organic chemistryOrganic ChemistryPlasmodium falciparumbiology.organism_classificationmedicine.diseaseProtein Structure Tertiary0104 chemical sciences030104 developmental biologyEnzymeCysteinedescription
A family of dipeptidyl enoates has been prepared and tested against the parasitic cysteine proteases rhodesain, cruzain and falcipain-2 related to sleeping sickness, Chagas disease and malaria, respectively. They have also been tested against human cathepsins B and L1 for selectivity. Dipeptidyl enoates resulted to be irreversible inhibitors of these enzymes. Some of the members of the family are very potent inhibitors of parasitic cysteine proteases displaying k2nd (M−1s−1) values of seven orders of magnitude. In vivo antiprotozoal testing was also performed. Inhibitors exhibited IC50 values in the micromolar range against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and even more promising lower values against Leishmania donovanii.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-09-01 | Bioorganic & Medicinal Chemistry |