Molecular Docking of 4-ethoxychalcones on Oxidoreductase/Pirin Inhibitors and Cytotoxic Evaluation on Breast/Skin Cancer Cell Lines

Author(s): Kishori Ramachandra Harshitha, Balladka Kunhanna Sarojini*, Badiadka Narayana, Anupam Glorious Lobo, Bhuvanesh Sukhlal Kalal

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 10 , 2020

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Graphical Abstract:


Background: The role of α, β unsaturated propenone derivatives, has attracted the chemists for its biological importance. An attempt is made to reveal the interaction between breast and skin cancer cell lines with the help of molecular docking studies.

Objective: The study aimed to synthesize and characterize 4-ethoxychalcones for testing breast and skin cancer targets.

Methods: A series of chalcone analogues starting from 4-ethoxyacetophenone and substituted aromatic aldehydes were synthesized, well-characterized and evaluated for their in vitro anticancer activities against human breast cancer (MDA-MB-231) and human metastatic melanoma (A-375) cell lines by MTT assay. Docking simulation was performed to study the drug-receptor interaction of chalcone scaffold on the active site of target inhibitor bound to cytochrome P450 family oxidoreductase for breast cancer and Pirin inhibiting target for skin cancer, respectively.

Results and Discussion: After performing cytotoxic evaluation, it was observed that compounds having a substitution at the para position showed better results compared to ortho and meta positions for both the cell lines. Molecular docking studies revealed different types of interactions with selected oxidoreductase and Pirin inhibiting targets. Ligand-protein interactions and morphological changes are monitored by molecular dynamics.

Conclusion: The presence of electron-withdrawing and donating groups on ring B marginally affected IC50 and docking scores. The stability of the binding mode of ligands having high inhibitory efficiency for compounds 8 and 10 predicted by docking studies was confirmed by molecular dynamics simulation. The pharmacokinetic parameters were found to be within the acceptable range. Further molecular dynamics study would provide the necessary information.

Keywords: Chalcones, spectral characterization, cytotoxic evaluation, molecular docking, molecular dynamics simulations, pharmacokinetics.

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Article Details

Year: 2020
Published on: 11 October, 2020
Page: [1245 - 1260]
Pages: 16
DOI: 10.2174/1570180817666200129143803
Price: $65

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