In Silico Antiprotozoal Evaluation of 1,4-Naphthoquinone Derivatives against Chagas and Leishmaniasis Diseases Using QSAR, Molecular Docking, and ADME Approaches
Chagas and leishmaniasis are two neglected diseases considered as public health problems worldwide, for which there is no effective, low-cost, and low-toxicity treatment for the host. Naphthoquinones are ligands with redox properties involved in oxidative biological processes with a wide variety of...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/6/687 |
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| author | Lina S. Prieto Cárdenas Karen A. Arias Soler Diana L. Nossa González Wilson E. Rozo Núñez Agobardo Cárdenas-Chaparro Pablo R. Duchowicz Jovanny A. Gómez Castaño |
| author_facet | Lina S. Prieto Cárdenas Karen A. Arias Soler Diana L. Nossa González Wilson E. Rozo Núñez Agobardo Cárdenas-Chaparro Pablo R. Duchowicz Jovanny A. Gómez Castaño |
| author_sort | Lina S. Prieto Cárdenas |
| collection | DOAJ |
| description | Chagas and leishmaniasis are two neglected diseases considered as public health problems worldwide, for which there is no effective, low-cost, and low-toxicity treatment for the host. Naphthoquinones are ligands with redox properties involved in oxidative biological processes with a wide variety of activities, including antiparasitic. In this work, in silico methods of quantitative structure–activity relationship (QSAR), molecular docking, and calculation of ADME (absorption, distribution, metabolism, and excretion) properties were used to evaluate naphthoquinone derivatives with unknown antiprotozoal activity. QSAR models were developed for predicting antiparasitic activity against <i>Trypanosoma cruzi</i>, <i>Leishmania amazonensis</i>, and <i>Leishmania infatum</i>, as well as the QSAR model for toxicity activity. Most of the evaluated ligands presented high antiparasitic activity. According to the docking results, the family of triazole derivatives presented the best affinity with the different macromolecular targets. The ADME results showed that most of the evaluated compounds present adequate conditions to be administered orally. Naphthoquinone derivatives show good biological activity results, depending on the substituents attached to the quinone ring, and perhaps the potential to be converted into drugs or starting molecules. |
| first_indexed | 2024-03-09T22:47:51Z |
| format | Article |
| id | doaj.art-dbcc595e39cb457e82af33db806ab67a |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:47:51Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-dbcc595e39cb457e82af33db806ab67a2023-11-23T18:27:03ZengMDPI AGPharmaceuticals1424-82472022-05-0115668710.3390/ph15060687In Silico Antiprotozoal Evaluation of 1,4-Naphthoquinone Derivatives against Chagas and Leishmaniasis Diseases Using QSAR, Molecular Docking, and ADME ApproachesLina S. Prieto Cárdenas0Karen A. Arias Soler1Diana L. Nossa González2Wilson E. Rozo Núñez3Agobardo Cárdenas-Chaparro4Pablo R. Duchowicz5Jovanny A. Gómez Castaño6Grupo Química-Física Molecular y Modelamiento Computacional (QUIMOL), Facultad de Ciencias, Universidad Pedagógica y Tecnológica de Colombia (UPTC), Avenida Central del Norte, Tunja 050030, ColombiaGrupo Química-Física Molecular y Modelamiento Computacional (QUIMOL), Facultad de Ciencias, Universidad Pedagógica y Tecnológica de Colombia (UPTC), Avenida Central del Norte, Tunja 050030, ColombiaGrupo Química-Física Molecular y Modelamiento Computacional (QUIMOL), Facultad de Ciencias, Universidad Pedagógica y Tecnológica de Colombia (UPTC), Avenida Central del Norte, Tunja 050030, ColombiaGrupo Química-Física Molecular y Modelamiento Computacional (QUIMOL), Facultad de Ciencias, Universidad Pedagógica y Tecnológica de Colombia (UPTC), Avenida Central del Norte, Tunja 050030, ColombiaGrupo Química-Física Molecular y Modelamiento Computacional (QUIMOL), Facultad de Ciencias, Universidad Pedagógica y Tecnológica de Colombia (UPTC), Avenida Central del Norte, Tunja 050030, ColombiaInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas, (CONICET—Universidad Nacional de La Plata), Diagonal 113 y Calle 64, C.C. 16, Sucursal 4, La Plata 1900, ArgentinaGrupo Química-Física Molecular y Modelamiento Computacional (QUIMOL), Facultad de Ciencias, Universidad Pedagógica y Tecnológica de Colombia (UPTC), Avenida Central del Norte, Tunja 050030, ColombiaChagas and leishmaniasis are two neglected diseases considered as public health problems worldwide, for which there is no effective, low-cost, and low-toxicity treatment for the host. Naphthoquinones are ligands with redox properties involved in oxidative biological processes with a wide variety of activities, including antiparasitic. In this work, in silico methods of quantitative structure–activity relationship (QSAR), molecular docking, and calculation of ADME (absorption, distribution, metabolism, and excretion) properties were used to evaluate naphthoquinone derivatives with unknown antiprotozoal activity. QSAR models were developed for predicting antiparasitic activity against <i>Trypanosoma cruzi</i>, <i>Leishmania amazonensis</i>, and <i>Leishmania infatum</i>, as well as the QSAR model for toxicity activity. Most of the evaluated ligands presented high antiparasitic activity. According to the docking results, the family of triazole derivatives presented the best affinity with the different macromolecular targets. The ADME results showed that most of the evaluated compounds present adequate conditions to be administered orally. Naphthoquinone derivatives show good biological activity results, depending on the substituents attached to the quinone ring, and perhaps the potential to be converted into drugs or starting molecules.https://www.mdpi.com/1424-8247/15/6/687chagasleishmaniasisnaphthoquinonesantiprotozoal evaluationQSARmolecular docking |
| spellingShingle | Lina S. Prieto Cárdenas Karen A. Arias Soler Diana L. Nossa González Wilson E. Rozo Núñez Agobardo Cárdenas-Chaparro Pablo R. Duchowicz Jovanny A. Gómez Castaño In Silico Antiprotozoal Evaluation of 1,4-Naphthoquinone Derivatives against Chagas and Leishmaniasis Diseases Using QSAR, Molecular Docking, and ADME Approaches Pharmaceuticals chagas leishmaniasis naphthoquinones antiprotozoal evaluation QSAR molecular docking |
| title | In Silico Antiprotozoal Evaluation of 1,4-Naphthoquinone Derivatives against Chagas and Leishmaniasis Diseases Using QSAR, Molecular Docking, and ADME Approaches |
| title_full | In Silico Antiprotozoal Evaluation of 1,4-Naphthoquinone Derivatives against Chagas and Leishmaniasis Diseases Using QSAR, Molecular Docking, and ADME Approaches |
| title_fullStr | In Silico Antiprotozoal Evaluation of 1,4-Naphthoquinone Derivatives against Chagas and Leishmaniasis Diseases Using QSAR, Molecular Docking, and ADME Approaches |
| title_full_unstemmed | In Silico Antiprotozoal Evaluation of 1,4-Naphthoquinone Derivatives against Chagas and Leishmaniasis Diseases Using QSAR, Molecular Docking, and ADME Approaches |
| title_short | In Silico Antiprotozoal Evaluation of 1,4-Naphthoquinone Derivatives against Chagas and Leishmaniasis Diseases Using QSAR, Molecular Docking, and ADME Approaches |
| title_sort | in silico antiprotozoal evaluation of 1 4 naphthoquinone derivatives against chagas and leishmaniasis diseases using qsar molecular docking and adme approaches |
| topic | chagas leishmaniasis naphthoquinones antiprotozoal evaluation QSAR molecular docking |
| url | https://www.mdpi.com/1424-8247/15/6/687 |
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