Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from <i>Entamoeba histolytica</i> and <i>Giardia lamblia</i> Identifies Inhibitors of Their Trophozoite Growth Phase
Infectious diseases caused by intestinal protozoan, such as <i>Entamoeba histolytica</i> (<i>E. histolytica</i>) and <i>Giardia lamblia</i> (<i>G. lamblia</i>) are a worldwide public health issue. They affect more than 70 million people every year. The...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/5943 |
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| author | Alfredo Juárez-Saldivar Elizabeth Barbosa-Cabrera Edgar E. Lara-Ramírez Alma D. Paz-González Ana V. Martínez-Vázquez Virgilio Bocanegra-García Isidro Palos Nuria E. Campillo Gildardo Rivera |
| author_facet | Alfredo Juárez-Saldivar Elizabeth Barbosa-Cabrera Edgar E. Lara-Ramírez Alma D. Paz-González Ana V. Martínez-Vázquez Virgilio Bocanegra-García Isidro Palos Nuria E. Campillo Gildardo Rivera |
| author_sort | Alfredo Juárez-Saldivar |
| collection | DOAJ |
| description | Infectious diseases caused by intestinal protozoan, such as <i>Entamoeba histolytica</i> (<i>E. histolytica</i>) and <i>Giardia lamblia</i> (<i>G. lamblia</i>) 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 <i>E. histolytica</i> and <i>G. lamblia</i>, 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 <i>G. lamblia</i> trophozoites (0.05–4.935 μg/mL), while folic acid showed activity against <i>E. histolytica</i> (0.186 μg/mL) and <i>G. lamblia</i> (5.342 μg/mL). |
| first_indexed | 2024-03-10T10:50:03Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:50:03Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b344c49328dc4deb8bf2fd0ce8502b632023-11-21T22:18:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211594310.3390/ijms22115943Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from <i>Entamoeba histolytica</i> and <i>Giardia lamblia</i> Identifies Inhibitors of Their Trophozoite Growth PhaseAlfredo Juárez-Saldivar0Elizabeth Barbosa-Cabrera1Edgar E. Lara-Ramírez2Alma D. Paz-González3Ana V. Martínez-Vázquez4Virgilio Bocanegra-García5Isidro Palos6Nuria E. Campillo7Gildardo Rivera8Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoSección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoUnidad de Investigación Biomédica de Zacatecas, Instituto Mexicano Del Seguro Social, Zacatecas 98617, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoCentro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoCentro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoUnidad Académica Multidisciplinaria Reynosa-Rodhe, Universidad Autónoma Tamaulipas, Carr. Reynosa-San Fernando, Reynosa 88779, MexicoCentro de Investigaciones Biológicas Margarita Salas (CIB-CSIC), Ramiro de Maeztu 9, 28040 Madrid, SpainLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoInfectious diseases caused by intestinal protozoan, such as <i>Entamoeba histolytica</i> (<i>E. histolytica</i>) and <i>Giardia lamblia</i> (<i>G. lamblia</i>) 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 <i>E. histolytica</i> and <i>G. lamblia</i>, 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 <i>G. lamblia</i> trophozoites (0.05–4.935 μg/mL), while folic acid showed activity against <i>E. histolytica</i> (0.186 μg/mL) and <i>G. lamblia</i> (5.342 μg/mL).https://www.mdpi.com/1422-0067/22/11/5943protozoaFDAvirtual screeningdrug repositioningmolecular docking |
| spellingShingle | Alfredo Juárez-Saldivar Elizabeth Barbosa-Cabrera Edgar E. Lara-Ramírez Alma D. Paz-González Ana V. Martínez-Vázquez Virgilio Bocanegra-García Isidro Palos Nuria E. Campillo Gildardo Rivera Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from <i>Entamoeba histolytica</i> and <i>Giardia lamblia</i> Identifies Inhibitors of Their Trophozoite Growth Phase International Journal of Molecular Sciences protozoa FDA virtual screening drug repositioning molecular docking |
| title | Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from <i>Entamoeba histolytica</i> and <i>Giardia lamblia</i> Identifies Inhibitors of Their Trophozoite Growth Phase |
| title_full | Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from <i>Entamoeba histolytica</i> and <i>Giardia lamblia</i> Identifies Inhibitors of Their Trophozoite Growth Phase |
| title_fullStr | Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from <i>Entamoeba histolytica</i> and <i>Giardia lamblia</i> Identifies Inhibitors of Their Trophozoite Growth Phase |
| title_full_unstemmed | Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from <i>Entamoeba histolytica</i> and <i>Giardia lamblia</i> Identifies Inhibitors of Their Trophozoite Growth Phase |
| title_short | Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from <i>Entamoeba histolytica</i> and <i>Giardia lamblia</i> Identifies Inhibitors of Their Trophozoite Growth Phase |
| title_sort | virtual screening of fda approved drugs against triose phosphate isomerase from i entamoeba histolytica i and i giardia lamblia i identifies inhibitors of their trophozoite growth phase |
| topic | protozoa FDA virtual screening drug repositioning molecular docking |
| url | https://www.mdpi.com/1422-0067/22/11/5943 |
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