Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as <i>Leishmania mexicana</i> Inhibitors
Cutaneous leishmaniasis (CL) is a public health problem affecting more than 98 countries worldwide. No vaccine is available to prevent the disease, and available medical treatments cause serious side effects. Additionally, treatment failure and parasite resistance have made the development of new dr...
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MDPI AG
2023-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/8/2046 |
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| author | Luis D. González-Morales Adriana Moreno-Rodríguez Lenci K. Vázquez-Jiménez Timoteo Delgado-Maldonado Alfredo Juárez-Saldivar Eyra Ortiz-Pérez Alma D. Paz-Gonzalez Edgar E. Lara-Ramírez Lilian Yépez-Mulia Patricia Meza Gildardo Rivera |
| author_facet | Luis D. González-Morales Adriana Moreno-Rodríguez Lenci K. Vázquez-Jiménez Timoteo Delgado-Maldonado Alfredo Juárez-Saldivar Eyra Ortiz-Pérez Alma D. Paz-Gonzalez Edgar E. Lara-Ramírez Lilian Yépez-Mulia Patricia Meza Gildardo Rivera |
| author_sort | Luis D. González-Morales |
| collection | DOAJ |
| description | Cutaneous leishmaniasis (CL) is a public health problem affecting more than 98 countries worldwide. No vaccine is available to prevent the disease, and available medical treatments cause serious side effects. Additionally, treatment failure and parasite resistance have made the development of new drugs against CL necessary. In this work, a virtual screening of natural products from the BIOFACQUIM and Selleckchem databases was performed using the method of molecular docking at the triosephosphate isomerase (TIM) enzyme interface of <i>Leishmania mexicana</i> (<i>L</i>. <i>mexicana</i>). Finally, the in vitro leishmanicidal activity of selected compounds against two strains of <i>L</i>. <i>mexicana</i>, their cytotoxicity, and selectivity index were determined. The top ten compounds were obtained based on the docking results. Four were selected for further in silico analysis. The ADME-Tox analysis of the selected compounds predicted favorable physicochemical and toxicological properties. Among these four compounds, <b>S-8</b> (IC<sub>50</sub> = 55 µM) demonstrated a two-fold higher activity against the promastigote of both <i>L. mexicana</i> strains than the reference drug glucantime (IC<sub>50</sub> = 133 µM). This finding encourages the screening of natural products as new anti-leishmania agents. |
| first_indexed | 2024-03-10T23:39:59Z |
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| id | doaj.art-dc3210e9930940d1a45fbb9da827b40b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T23:39:59Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-dc3210e9930940d1a45fbb9da827b40b2023-11-19T02:35:54ZengMDPI AGPharmaceutics1999-49232023-07-01158204610.3390/pharmaceutics15082046Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as <i>Leishmania mexicana</i> InhibitorsLuis D. González-Morales0Adriana Moreno-Rodríguez1Lenci K. Vázquez-Jiménez2Timoteo Delgado-Maldonado3Alfredo Juárez-Saldivar4Eyra Ortiz-Pérez5Alma D. Paz-Gonzalez6Edgar E. Lara-Ramírez7Lilian Yépez-Mulia8Patricia Meza9Gildardo Rivera10Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoLaboratorio de Estudios Epidemiológicos, Clínicos, Diseños Experimentales e Investigación, Facultad de Ciencias Químicas, Universidad Autónoma “Benito Juárez” de Oaxaca, Avenida Universidad S/N, Ex Hacienda Cinco Señores, Oaxaca 68120, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoUnidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias-Pediatría, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoUnidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias-Pediatría, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoCutaneous leishmaniasis (CL) is a public health problem affecting more than 98 countries worldwide. No vaccine is available to prevent the disease, and available medical treatments cause serious side effects. Additionally, treatment failure and parasite resistance have made the development of new drugs against CL necessary. In this work, a virtual screening of natural products from the BIOFACQUIM and Selleckchem databases was performed using the method of molecular docking at the triosephosphate isomerase (TIM) enzyme interface of <i>Leishmania mexicana</i> (<i>L</i>. <i>mexicana</i>). Finally, the in vitro leishmanicidal activity of selected compounds against two strains of <i>L</i>. <i>mexicana</i>, their cytotoxicity, and selectivity index were determined. The top ten compounds were obtained based on the docking results. Four were selected for further in silico analysis. The ADME-Tox analysis of the selected compounds predicted favorable physicochemical and toxicological properties. Among these four compounds, <b>S-8</b> (IC<sub>50</sub> = 55 µM) demonstrated a two-fold higher activity against the promastigote of both <i>L. mexicana</i> strains than the reference drug glucantime (IC<sub>50</sub> = 133 µM). This finding encourages the screening of natural products as new anti-leishmania agents.https://www.mdpi.com/1999-4923/15/8/2046<i>Leishmania</i>triosephosphate isomerasemolecular dockingnatural productsvirtual screening |
| spellingShingle | Luis D. González-Morales Adriana Moreno-Rodríguez Lenci K. Vázquez-Jiménez Timoteo Delgado-Maldonado Alfredo Juárez-Saldivar Eyra Ortiz-Pérez Alma D. Paz-Gonzalez Edgar E. Lara-Ramírez Lilian Yépez-Mulia Patricia Meza Gildardo Rivera Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as <i>Leishmania mexicana</i> Inhibitors Pharmaceutics <i>Leishmania</i> triosephosphate isomerase molecular docking natural products virtual screening |
| title | Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as <i>Leishmania mexicana</i> Inhibitors |
| title_full | Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as <i>Leishmania mexicana</i> Inhibitors |
| title_fullStr | Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as <i>Leishmania mexicana</i> Inhibitors |
| title_full_unstemmed | Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as <i>Leishmania mexicana</i> Inhibitors |
| title_short | Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as <i>Leishmania mexicana</i> Inhibitors |
| title_sort | triose phosphate isomerase structure based virtual screening and in vitro biological activity of natural products as i leishmania mexicana i inhibitors |
| topic | <i>Leishmania</i> triosephosphate isomerase molecular docking natural products virtual screening |
| url | https://www.mdpi.com/1999-4923/15/8/2046 |
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