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Current Computer-Aided Drug Design

Editor-in-Chief

ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Potential Aromatase Inhibitors from Centella asiatica with Non-synonymous SNPS - A Computational Approach

Author(s): Sheshadri S Temkar, Amruta Sridhara, Dhrithi Jayasimha Mallur, Deepak Ishwara Shivaprakash, Divya Iyengar, Nritam Das and Benedict Paul C*

Volume 20, Issue 4, 2024

Published on: 15 June, 2023

Page: [341 - 358] Pages: 18

DOI: 10.2174/1573409919666230525151933

Price: $65

Abstract

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: rs700519, rs78310315 and rs56658716.

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 compounds with the native and mutated conformations showed that out of the obtained fourteen phytocompounds, Isoquercetin, Quercetin and 9H-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-Fluorene-2-carboxylic acid, providing better lead compounds for further evaluation as potential aromatase inhibitors.

Keywords: Centella asiatica, aromatase inhibitors, breast cancer, molecular docking simulations, single nucleotide polymorphism, force field energy profile, ADMET studies.

Graphical Abstract
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