Potential Aromatase Inhibitors from Centella asiatica with Non-synonymous SNPS - A Computational Approach
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Aromatase inhibitors are used in the treatment of breast cancer as they are effective in decreasing the concentration of estrogen. As SNPs impact the efficacy or toxicity of drugs, evaluating them with mutated conformations would help in identifying potential inhibitors. In recent years, phytocompounds have been under scrutiny for their activity as potential inhibitors.
OBJECTIVE: In this study, we have evaluated Centella asiatica compounds for their activity on aromatase with clinically significant SNPs: rs</i>700519, rs</i>78310315 and rs</i>56658716.
METHODS: Using AMDock v.1.5.2, which uses the AutoDock Vina engine, molecular docking simulations were carried out, and the docked complexes were analyzed for their chemical interactions such as polar contacts using PyMol v2.5. The mutated conformations of the protein and force field energy differences were computationally derived using SwissPDB Viewer. PubChem, dbSNP and ClinVar databases were used to retrieve the compounds and SNPs. ADMET prediction profile was generated using admetSAR v1.0.
RESULTS: Docking simulations of the C. asiatica</i> compounds with the native and mutated conformations showed that out of the obtained fourteen phytocompounds, Isoquercetin, Quercetin and 9H</i>-Fluorene-2-carboxylic acid were able to dock with best scores in terms of binding affinity (- 8.4kcal/mol), Estimated Ki (0.6 μM) values and Polar Contacts in both native and mutated conformations (3EQM, 5JKW, 3S7S).
CONCLUSION: Our computational analyses predict that the deleterious SNPs did not impact the molecular interactions of Isoquercetin, Quercetin and 9H</i>-Fluorene-2-carboxylic acid, providing better lead compounds for further evaluation as potential aromatase inhibitors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Current computer-aided drug design - 20(2023), 4 vom: 25., Seite 341-358 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Temkar, Sheshadri S [VerfasserIn] |
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| Links: |
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| Themen: |
ADMET studies |
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| Anmerkungen: |
Date Revised 13.10.2023 published: Print Citation Status Publisher |
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| doi: |
10.2174/1573409919666230525151933 |
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| Förderinstitution / Projekttitel: |
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NLM357340094 |
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| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Aromatase inhibitors are used in the treatment of breast cancer as they are effective in decreasing the concentration of estrogen. As SNPs impact the efficacy or toxicity of drugs, evaluating them with mutated conformations would help in identifying potential inhibitors. In recent years, phytocompounds have been under scrutiny for their activity as potential inhibitors | ||
| 520 | |a OBJECTIVE: In this study, we have evaluated Centella asiatica compounds for their activity on aromatase with clinically significant SNPs: rs</i>700519, rs</i>78310315 and rs</i>56658716 | ||
| 520 | |a METHODS: Using AMDock v.1.5.2, which uses the AutoDock Vina engine, molecular docking simulations were carried out, and the docked complexes were analyzed for their chemical interactions such as polar contacts using PyMol v2.5. The mutated conformations of the protein and force field energy differences were computationally derived using SwissPDB Viewer. PubChem, dbSNP and ClinVar databases were used to retrieve the compounds and SNPs. ADMET prediction profile was generated using admetSAR v1.0 | ||
| 520 | |a RESULTS: Docking simulations of the C. asiatica</i> compounds with the native and mutated conformations showed that out of the obtained fourteen phytocompounds, Isoquercetin, Quercetin and 9H</i>-Fluorene-2-carboxylic acid were able to dock with best scores in terms of binding affinity (- 8.4kcal/mol), Estimated Ki (0.6 μM) values and Polar Contacts in both native and mutated conformations (3EQM, 5JKW, 3S7S) | ||
| 520 | |a CONCLUSION: Our computational analyses predict that the deleterious SNPs did not impact the molecular interactions of Isoquercetin, Quercetin and 9H</i>-Fluorene-2-carboxylic acid, providing better lead compounds for further evaluation as potential aromatase inhibitors | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Centella asiatica</i> | |
| 650 | 4 | |a aromatase inhibitors | |
| 650 | 4 | |a breast cancer | |
| 650 | 4 | |a force field energy profile | |
| 650 | 4 | |a molecular docking simulations | |
| 650 | 4 | |a single nucleotide polymorphism | |
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| 700 | 1 | |a Shivaprakash, Deepak Ishwara |e verfasserin |4 aut | |
| 700 | 1 | |a Iyengar, Divya |e verfasserin |4 aut | |
| 700 | 1 | |a Das, Nritam |e verfasserin |4 aut | |
| 700 | 1 | |a C, Benedict Paul |e verfasserin |4 aut | |
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