1. Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from Entamoeba histolytica and Giardia lamblia Identifies Inhibitors of Their Trophozoite Growth Phase
- Author
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Gildardo Rivera, Isidro Palos, Elizabeth Barbosa-Cabrera, Virgilio Bocanegra-García, Nuria E. Campillo, Alfredo Juárez-Saldivar, Ana Verónica Martínez-Vázquez, Alma D Paz-González, Edgar E. Lara-Ramírez, Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional (México), Juárez-Saldivar, Alfredo, Barbosa-Cabrera, Elizabeth, Lara-Ramírez, Edgar E., Paz-González, Alma D., Bocanegra-García, Virgilio, Palos, Isidro, Campillo, Nuria E., Rivera, Gildardo, Juárez-Saldivar, Alfredo [0000-0002-4059-7361], Barbosa-Cabrera, Elizabeth [0000-0002-7111-7922], Lara-Ramírez, Edgar E. [0000-0001-7112-3233], Paz-González, Alma D. [0000-0002-0938-6304], Bocanegra-García, Virgilio [0000-0002-0728-2018], Palos, Isidro [0000-0003-0124-531X], Campillo, Nuria E. [0000-0002-9948-2665], and Rivera, Gildardo [0000-0001-9842-4167]
- Subjects
Virtual screening ,0301 basic medicine ,medicine.drug_class ,QH301-705.5 ,030106 microbiology ,drug repositioning ,medicine.disease_cause ,Catalysis ,Microbiology ,Triosephosphate isomerase ,Inorganic Chemistry ,03 medical and health sciences ,Entamoeba histolytica ,fluids and secretions ,parasitic diseases ,medicine ,Giardia lamblia ,Physical and Theoretical Chemistry ,Protozoa ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,chemistry.chemical_classification ,biology ,Drug repositioning ,Organic Chemistry ,General Medicine ,molecular docking ,biology.organism_classification ,virtual screening ,digestive system diseases ,Computer Science Applications ,Diarrhea ,Metronidazole ,Chemistry ,030104 developmental biology ,Enzyme ,chemistry ,Molecular docking ,Antiprotozoal ,medicine.symptom ,FDA ,medicine.drug - Abstract
8 p.-3 fig.-1 tab., Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure-based virtual screening of FDA-approved drugs was performed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05–4.935 μg/mL), while folic acid showed activity against E. histolytica (0.186 μg/mL) and G. lamblia (5.342 μg/mL)., This research was funded by the Secretaria de Investigación y Posgrado del Instituto Politécnico Nacional, grant number 20210050.
- Published
- 2021