Molecular docking based screening of novel designed chalcone series of compounds for their anti-cancer activity
Chennu Maruthi Malya Prasada Rao1, Rajendra Prasad Yejella2, Rehman Shaik Abdul Rehman3
1Research Scholar, Department of Pharmaceutical Sciences, JNTUK, Kakinada-533003, Andhra Pradesh, India.
Abstract:
Epidermal growth factor receptors (EGFR) are critical for the growth of many tumors and expressed at high levels in about one third of epithelial cancers. Hence, blockade of the binding sites for EGFR has been hypothesized as an effective anti-cancer therapy. Chalcone derivative compounds have been shown to be highly effective anti-cancer agents, however there are still so many novel derivatives possible, one of which might get us the best targeted EGFR inhibitor. In this effort directed towards the discovery of novel, potent anti-tumor agents for the treatment of cancer, in the present study a library of novel chalcone series of compounds has been designed and evaluated for their anti-cancer activity targeting EGFR kinase domain using various computational approaches. Among the twenty five novel designed chalcone series of compounds, all of them have found to be successfully docking inside the active binding domain of EGFR receptor target with a binding energy in a range of -6.10 to -9.25 Kcal/mol with predicted IC50 value range of 33.50 micor molar to 164.66 nano molar respectively. On the other hand, calculated 2DQSAR molecular descriptor properties of the compounds showed promising ADME parameters and found to be well in compliance with Lipinski׳s rule of five. Among all the twenty five compounds tested, compound 21 ((2E)-3-(anthracen-9-yl)-1-phenylprop-2-2n-1- one) was found to be the best lead like molecule with a binding energy of -9.25 kcal/mol with predicted IC50 value of 164.66 nano molar. Conclusively, novel designed compound 21 of the present study have shown promising anti-cancer potential worth considering for further evaluations.
Insights
Researchers designed novel chalcone compounds as potential anti-cancer drugs targeting the epidermal growth factor receptor (EGFR). Compound 21 showed the most promise, demonstrating significant binding affinity and potential for further development.
Area of Science:
- Medicinal Chemistry
- Computational Drug Design
- Oncology
Background:
- Epidermal growth factor receptor (EGFR) is crucial for tumor growth and overexpressed in many epithelial cancers.
- Targeting EGFR is a key strategy in anti-cancer therapy.
- Chalcone derivatives are known for their anti-cancer properties, prompting exploration of novel derivatives.
Purpose of the Study:
- To design and computationally evaluate a novel series of chalcone compounds as potential EGFR inhibitors.
- To identify lead compounds with high binding affinity and favorable drug-like properties for cancer treatment.
Main Methods:
- Design of a library of 25 novel chalcone compounds.
- Molecular docking simulations to assess binding to the EGFR kinase domain.
- 2D Quantitative Structure-Activity Relationship (2DQSAR) analysis for ADME properties and Lipinski's rule compliance.
Main Results:
- All 25 designed chalcone compounds successfully docked into the EGFR active site, with binding energies ranging from -6.10 to -9.25 Kcal/mol.
- Predicted IC50 values ranged from 33.50 µM to 164.66 nM.
- Compound 21 exhibited the highest binding energy (-9.25 Kcal/mol) and a low predicted IC50 (164.66 nM), alongside favorable ADME properties compliant with Lipinski's rule.
Conclusions:
- Novel chalcone derivatives show significant potential as targeted anti-cancer agents against EGFR.
- Compound 21 is identified as a promising lead molecule for further preclinical evaluation and development.
- Computational approaches are effective in discovering novel EGFR inhibitors with favorable drug-like characteristics.
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