Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp [version 3; peer review: 1 approved, 2 approved with reservations]
Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Methods: Hence, this study aims to screen for natural products' structural analog...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2023-07-01
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| Online Access: | https://f1000research.com/articles/12-93/v3 |
| _version_ | 1797780743595753472 |
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| author | Luis Daniel Goyzueta-Mamani Mayron Antonio Candia Puma Miguel Angel Chávez-Fumagalli Haruna Luz Barazorda-Ccahuana Daniela Pagliara Lage Eduardo Antonio Ferraz Coelho Camila Simões de Freitas Grasiele de Sousa Vieria Tavares |
| author_facet | Luis Daniel Goyzueta-Mamani Mayron Antonio Candia Puma Miguel Angel Chávez-Fumagalli Haruna Luz Barazorda-Ccahuana Daniela Pagliara Lage Eduardo Antonio Ferraz Coelho Camila Simões de Freitas Grasiele de Sousa Vieria Tavares |
| author_sort | Luis Daniel Goyzueta-Mamani |
| collection | DOAJ |
| description | Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Methods: Hence, this study aims to screen for natural products' structural analogs as new drug candidates against leishmaniasis. We applied Computer-aided drug design (CADD) approaches, such as virtual screening, molecular docking, molecular dynamics simulation, molecular mechanics–generalized Born surface area (MM–GBSA) binding free estimation, and free energy perturbation (FEP) aiming to select structural analogs from natural products that have shown anti-leishmanial and anti-arginase activities and that could bind selectively against the Leishmania arginase enzyme. Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, and malvidin showed good results against arginase targets from three parasite species and negative results for potential toxicities. The echioidinin and malvidin ligands generated interactions in the active center at pH 2.0 conditions by MM-GBSA and FEP methods. Conclusions: This work suggests the potential anti-leishmanial activity of the compounds and thus can be further in vitro and in vivo experimentally validated. |
| first_indexed | 2024-03-12T23:48:10Z |
| format | Article |
| id | doaj.art-2f4bee29b81f469cb547dcd79780949e |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-03-12T23:48:10Z |
| publishDate | 2023-07-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-2f4bee29b81f469cb547dcd79780949e2023-07-14T00:00:01ZengF1000 Research LtdF1000Research2046-14022023-07-0112152921Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp [version 3; peer review: 1 approved, 2 approved with reservations]Luis Daniel Goyzueta-Mamani0https://orcid.org/0000-0003-0308-1160Mayron Antonio Candia Puma1https://orcid.org/0000-0002-6328-3840Miguel Angel Chávez-Fumagalli2https://orcid.org/0000-0002-8394-4802Haruna Luz Barazorda-Ccahuana3https://orcid.org/0000-0001-8791-0506Daniela Pagliara Lage4Eduardo Antonio Ferraz Coelho5Camila Simões de Freitas6https://orcid.org/0000-0001-7882-215XGrasiele de Sousa Vieria Tavares7Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Catolica de Santa Maria de Arequipa, Arequipa, PeruComputational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Catolica de Santa Maria de Arequipa, Arequipa, PeruComputational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Catolica de Santa Maria de Arequipa, Arequipa, PeruComputational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Catolica de Santa Maria de Arequipa, Arequipa, PeruUniversidade Federal de Minas Gerais, Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Belo Horizonte, Minas Gerais, BrazilUniversidade Federal de Minas Gerais, Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Belo Horizonte, Minas Gerais, BrazilUniversidade Federal de Minas Gerais, Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Belo Horizonte, Minas Gerais, BrazilUniversidade Federal de Minas Gerais, Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Belo Horizonte, Minas Gerais, BrazilIntroduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Methods: Hence, this study aims to screen for natural products' structural analogs as new drug candidates against leishmaniasis. We applied Computer-aided drug design (CADD) approaches, such as virtual screening, molecular docking, molecular dynamics simulation, molecular mechanics–generalized Born surface area (MM–GBSA) binding free estimation, and free energy perturbation (FEP) aiming to select structural analogs from natural products that have shown anti-leishmanial and anti-arginase activities and that could bind selectively against the Leishmania arginase enzyme. Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, and malvidin showed good results against arginase targets from three parasite species and negative results for potential toxicities. The echioidinin and malvidin ligands generated interactions in the active center at pH 2.0 conditions by MM-GBSA and FEP methods. Conclusions: This work suggests the potential anti-leishmanial activity of the compounds and thus can be further in vitro and in vivo experimentally validated.https://f1000research.com/articles/12-93/v3leishmaniasis Leishmania arginase computer-aided drug design molecular dynamics simulation antiprotozoal agents; drug discoveryeng |
| spellingShingle | Luis Daniel Goyzueta-Mamani Mayron Antonio Candia Puma Miguel Angel Chávez-Fumagalli Haruna Luz Barazorda-Ccahuana Daniela Pagliara Lage Eduardo Antonio Ferraz Coelho Camila Simões de Freitas Grasiele de Sousa Vieria Tavares Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp [version 3; peer review: 1 approved, 2 approved with reservations] F1000Research leishmaniasis Leishmania arginase computer-aided drug design molecular dynamics simulation antiprotozoal agents; drug discovery eng |
| title | Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp [version 3; peer review: 1 approved, 2 approved with reservations] |
| title_full | Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp [version 3; peer review: 1 approved, 2 approved with reservations] |
| title_fullStr | Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp [version 3; peer review: 1 approved, 2 approved with reservations] |
| title_full_unstemmed | Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp [version 3; peer review: 1 approved, 2 approved with reservations] |
| title_short | Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp [version 3; peer review: 1 approved, 2 approved with reservations] |
| title_sort | computer aided drug design approaches applied to screen natural product s structural analogs targeting arginase in leishmania spp version 3 peer review 1 approved 2 approved with reservations |
| topic | leishmaniasis Leishmania arginase computer-aided drug design molecular dynamics simulation antiprotozoal agents; drug discovery eng |
| url | https://f1000research.com/articles/12-93/v3 |
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