Computational investigation of turmeric phytochemicals targeting PTR1 enzyme of Leishmania species
© 2024 The Authors..
In this study, we used in silico techniques to identify available parasite treatments, representing a promising therapeutic avenue. Building upon our computational initiatives aimed at discovering natural inhibitors for various target enzymes from parasites causing neglected tropical diseases (NTDs), we present novel findings on three turmeric-derived phytochemicals as inhibitors of Leishmania pteridine reductase I (PTR1) through in silico methodologies. PTR1, a crucial enzyme in the unique folate metabolism of trypanosomatid parasites, holds established therapeutic significance. Employing MOE software, a molecular docking analysis assesses the efficacy of turmeric phytochemicals against Leishmania PTR1. Validation of the docking protocol is confirmed with an RMSD value of 2. Post-docking, compounds displaying notable interactions with critical residues and binding affinities ranging between -6 and -8 kcal/mol are selected for interaction pattern exploration. Testing twelve turmeric phytochemicals, including curcumin, zingiberene, curcumol, curcumenol, eugenol, bisdemethoxycurcumin, tetrahydrocurcumin, tryethylcurcumin, turmerones, turmerin, demethoxycurcumin, and turmeronols, revealed binding affinities ranging from -5.5 to -8 kcal/mol. Notably, curcumin, demethoxycurcumin, and bisdemethoxycurcumin exhibit binding affinities within -6.5 to -8 kcal/mol and establish substantial interactions with catalytic residues. These phytochemicals hold promise as lead structures for rational drug design targeting Leishmania spp. PTR in future applications. This work underscores the potential of these identified phytochemicals in the development of more effective inhibitors, demonstrating their relevance in addressing neglected tropical diseases caused by parasites.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Heliyon - 10(2024), 6 vom: 30. März, Seite e27907 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ullah, Wasia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 28.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.heliyon.2024.e27907 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370225651 |
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| 520 | |a In this study, we used in silico techniques to identify available parasite treatments, representing a promising therapeutic avenue. Building upon our computational initiatives aimed at discovering natural inhibitors for various target enzymes from parasites causing neglected tropical diseases (NTDs), we present novel findings on three turmeric-derived phytochemicals as inhibitors of Leishmania pteridine reductase I (PTR1) through in silico methodologies. PTR1, a crucial enzyme in the unique folate metabolism of trypanosomatid parasites, holds established therapeutic significance. Employing MOE software, a molecular docking analysis assesses the efficacy of turmeric phytochemicals against Leishmania PTR1. Validation of the docking protocol is confirmed with an RMSD value of 2. Post-docking, compounds displaying notable interactions with critical residues and binding affinities ranging between -6 and -8 kcal/mol are selected for interaction pattern exploration. Testing twelve turmeric phytochemicals, including curcumin, zingiberene, curcumol, curcumenol, eugenol, bisdemethoxycurcumin, tetrahydrocurcumin, tryethylcurcumin, turmerones, turmerin, demethoxycurcumin, and turmeronols, revealed binding affinities ranging from -5.5 to -8 kcal/mol. Notably, curcumin, demethoxycurcumin, and bisdemethoxycurcumin exhibit binding affinities within -6.5 to -8 kcal/mol and establish substantial interactions with catalytic residues. These phytochemicals hold promise as lead structures for rational drug design targeting Leishmania spp. PTR in future applications. This work underscores the potential of these identified phytochemicals in the development of more effective inhibitors, demonstrating their relevance in addressing neglected tropical diseases caused by parasites | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Binding affinities | |
| 650 | 4 | |a Enzyme inhibition | |
| 650 | 4 | |a In silico techniques | |
| 650 | 4 | |a Leishmania pteridine reductase I (PTR1) | |
| 650 | 4 | |a Molecular docking analysis | |
| 650 | 4 | |a Neglected tropical diseases | |
| 650 | 4 | |a Parasite treatments | |
| 650 | 4 | |a Rational drug design | |
| 650 | 4 | |a Therapeutic potential | |
| 650 | 4 | |a Turmeric-derived phytochemicals | |
| 700 | 1 | |a Wu, Wen-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Malak, Nosheen |e verfasserin |4 aut | |
| 700 | 1 | |a Nasreen, Nasreen |e verfasserin |4 aut | |
| 700 | 1 | |a Swelum, Ayman A |e verfasserin |4 aut | |
| 700 | 1 | |a Marcelino, Liliana Aguilar |e verfasserin |4 aut | |
| 700 | 1 | |a Niaz, Sadaf |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Adil |e verfasserin |4 aut | |
| 700 | 1 | |a Ben Said, Mourad |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chien-Chin |e verfasserin |4 aut | |
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