TARGET-ORIENTED MOLECULAR DOCKING AND ADMET ANALYSIS OF NOVEL CHALCONE-LINKED QUINOLINE DERIVATIVES FOR CANCER THERAPY
DOI:
https://doi.org/10.22159/ajpcr.2025v18i9.55390Keywords:
Structure-activity relationship, Molecular docking, Chalcone lined quinolines, anticancer agents, Absorption, distribution, metabolism, excretionAbstract
Objective: Molecular docking studies were carried out on thirty-three novel chalcone-linked quinoline derivatives to evaluate their potential as anticancer drug candidates targeting EGFR tyrosine kinase.
Methods: The computational study was executed using the Maestro interface in the Schrodinger to target EGFR enzyme (PDB ID: 4HJO). For all the compounds, molecular docking was subjected to ADME analysis using QikProp module.
Results: Analysis of protein-ligand interactions demonstrated that the most active compounds formed stable hydrogen bonds with key residues PHE-832, THR-830, SER-676, THR-766, MET-796, CYS-751, GLN-767 and ASN-818 in the EGFR binding pocket. ADMET predictions indicated favorable drug-like properties for all compounds, with acceptable molecular weights range of ≤500 Da, optimal lipophilicity (LogP< 5), and high gastrointestinal absorption rates. The compounds showed compliance with Lipinski’s rule of five and exhibited blood-brain barrier permeability.
Conclusion: The targeting of EGFR tyrosine kinase by these derivatives indicates potential effectiveness of chalcone linked quinoline derivatives.
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References
1. Hassanpour SH, Dehghani M. Review of cancer from perspective of molecular. J Cancer Res Pract. 2017 Dec;4(4):127-9. doi: 10.1016/j. jcrpr.2017.07.001
2. Mehdi S, Chauhan A, Dhutty A. Cancer and new prospective to treat cancer. Int J Curr Pharm Res. 2023 Oct;15(6):16-22. doi: 10.22159/ ijcpr.2023v15i6.3078
3. Upadhyay A. Cancer: An unknown territory; Rethinking before going ahead. Genes Dis. 2020 Sep 18;8(5):655-61. doi: 10.1016/j. gendis.2020.09.002
4. Sharma AK, Naruka PS, Soni SL, Sharma V, Madaan V, Sharma M. Covid-19: A review report. Int J Curr Pharm Res. 2022 Feb;14(1):17-22.
5. Mir MA, Banik BK. Heterocyclic phytochemicals as anticancer agents. Curr Top Med Chem. 2025;25(5):533-53. doi: 10.2174/011568026631 4693240914070250
6. Hossain M, Habib I, Singha K, Kumar A. FDA-approved heterocyclic molecules for cancer treatment: Synthesis, dosage, mechanism of action and their adverse effect. Heliyon. 2024 Jan;10(1):e23172. doi: 10.1016/j.heliyon.2023.e23172
7. Gupta SK, Mishra A. Synthesis, characterization and screening for anti-inflammatory and analgesic activity of quinoline derivatives bearingazetidinones scaffolds. Antiinflamm Antiallergy Agents Med Chem. 2016;15(1):31-43. doi: 10.2174/1871523015666160210124545
8. Shang XF, Morris-Natschke SL, Liu YQ, Guo X, Xu XS, Goto M, et al. Biologically active quinoline and quinazoline alkaloids Part I. Med Res Rev. 2018;38(3):775-828. doi: 10.1002/med.21466
9. Dawoud NT, El-Fakharany EM, Abdallah AE, El-Gendi H, Lofty DR. Synthesis, and docking studies of novel heterocycles incorporating the indazolylthiazole moiety as antimicrobial and anticancer agents. Sci Rep. 2022 Mar;12:3424. doi: 10.1038/s41598-022-07456-1
10. Kumar A, Singh AK, Singh H, Vijayan V, Kumar D, Naik J, et al. Nitrogen containing heterocycles as anticancer agents: A medicinal chemistry perspective. Pharmaceuticals (Basel). 2023 Feb 14;16(2):299. doi: 10.3390/ph16020299
11. Dhaliwal JS, Moshawih S, Goh KW, Loy ML, Hossain S, Hermansyah A, et al. Pharmacotherapeutics applications and chemistry of chalcone derivatives. Molecules. 2022 Oct;27(20):7062. doi: 10.3390/molecules27207062
12. Salehi B, Quispe C, Chamkhi I, Omari NE, Balahbib A, Sharifi-Rad J, et al. Pharmacological properties of chalcones: A review of preclinical including molecular mechanisms and clinical evidence. Front Pharmacol. 2021 Jan 18;11:592654. doi: 10.3389/fphar.2020.592654
13. Venkatarao V, Kumar L, Jha A, Sridhar G. Synthesis and biological evaluation of chalcone fused quinoline derivatives as anticancer agents. Chem Data Collect. 2019 May;22:100236. doi: 10.1016/j. cdc.2019.100236
14. Atukuri D, Vijayalaxmi S, Sanjeevamurthy R, Vidya L, Prasannakumar R, Raghavendra MM. Identification of quinoline-chalcones and heterocyclic chalcone-appended quinolines as broad-spectrum pharmacological agents. Bioorg Chem. 2020 Dec;105:104419. doi: 10.1016/j.bioorg.2020.104419
15. Park JH, Liu Y, Lemmon MA, Radhakrishan R. Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain. Biochem J. 2012;448(3):417-23. doi: 10.1042/bj20121513
16. Mamatha P, Bhikshapathi DV. Determination of in vitro cytotoxicity of entrectinib and pemigatinib nanosponges tablets on a 498, MCF-7 and PANC-1 cell lines. Int J Pharm Pharm Sci. 2004 Dec;16(2):12-6. doi: 10.22159/ijpps.2024v16i2.49567
17. Thomas K. In silico screening by molecular docking of heterocyclic compounds with furan or indole nucleus from database for anticancer activity and validation of the method by redocking. Int J Pharm Pharm Sci. 2004 Apr;16:42-5. doi: 10.22159/ijpps.2024v16i4.50478
18. Franco BB, Agilandeswari P, Karthik L. Computational screening of potent anti-inflammatory compounds for human mitogen-activated protein kinase: A comprehensive and combined in silico approach. Int J Curr Pharm Res. 2024 Oct;16(6):21-32. doi: 10.22159/ ijcpr.2024v16i6.6023
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Copyright (c) 2025 Tejinder Kaur, Divya Dhawal Bhandari, Rajiv Sharma, Yash Pal Singh, Subham Das
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