Computer-aided drug design approaches applied to screen natural product's structural analogs targeting arginase in Leishmania spp
Copyright: © 2023 Barazorda-Ccahuana HL et al..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
F1000Research - 12(2023) vom: 28., Seite 93 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Barazorda-Ccahuana, Haruna Luz [VerfasserIn] |
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| Links: |
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| Themen: |
Antiprotozoal agents; drug discovery |
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| Anmerkungen: |
Date Completed 19.07.2023 Date Revised 24.07.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.12688/f1000research.129943.3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359257909 |
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| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright: © 2023 Barazorda-Ccahuana HL et al. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Leishmania arginase | |
| 650 | 4 | |a antiprotozoal agents; drug discovery | |
| 650 | 4 | |a computer-aided drug design | |
| 650 | 4 | |a leishmaniasis | |
| 650 | 4 | |a molecular dynamics simulation | |
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| 700 | 1 | |a Candia Puma, Mayron Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Simões de Freitas, Camila |e verfasserin |4 aut | |
| 700 | 1 | |a de Sousa Vieria Tavares, Grasiele |e verfasserin |4 aut | |
| 700 | 1 | |a Pagliara Lage, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Ferraz Coelho, Eduardo Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Chávez-Fumagalli, Miguel Angel |e verfasserin |4 aut | |
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