Document Type : Original Research Article


Department of chemistry, Faculty of physical sciences, Ahmadu Bello University, Zaria, Kaduna, Nigeria


Despite advancements in analytics and therapy, breast cancer remains one of the leading causes of death and the second most prevalent cancer among women worldwide. This study focuses on the development of more potent and safer coumarin derivatives as anti-breast cancer agents. The design process involved molecular docking studies and structural modifications based on a design template. The docking studies involved 26 coumarin derivatives and the active site residues of VEGFR-2 target protein. Among the compounds tested, compound 7 demonstrated a higher docking score (-149.893 kcal/mol) compared to Sorafenib (-144.289 kcal/mol), which served as the design template. By introducing electron-rich -NH2 and -OH groups to the various positions on the template, resulting in increased electron density and basic character, five novel derivatives with improved binding affinities (-156.185 to -171.985 kcal/mol) were designed. Consequently, these compounds exhibit enhanced binding capabilities compared to Sorafenib. Moreover, pharmacological studies indicate that the designed derivatives possess drug-like qualities and favorable ADMET profiles. As a result, these research findings hold promise for the discovery of new and improved drugs for the treatment of breast cancer.

Graphical Abstract

Molecular docking studies of some coumarin derivatives as anti-breast cancer agents: Computer-aided design and pharmacokinetics studies


Main Subjects

  1. References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018, CA: a cancer journal for clinicians; 2018 Jan; 68(1):7-30.
    2. Balani S, Nguyen LV, Eaves CJ. Modeling the process of human tumorigenesis, Nature communications; 2017 May 25; 8(1):15422.
    3. Setrerrahmane S, Xu H. Tumor-related interleukins: old validated targets for new anti-cancer drug development, Molecular cancer; 2017 Dec; 16(1):1-7.


    1. Godoy AS, Chung I, Montecinos VP, Buttyan R, Johnson CS, Smith GJ. Role of androgen and vitamin D receptors in endothelial cells from benign and malignant human prostate, American Journal of Physiology-Endocrinology and Metabolism; 2013 Jun 1; 304(11):E1131-9.
    2. Russo G, Mischi M, Scheepens W, De la Rosette JJ, Wijkstra H. Angiogenesis in prostate cancer: onset, progression and imaging, BJU international; 2012 Dec; 110(11c):E794-808. 
    3. Cabebe E, Wakelee H. Sunitinib: a newly approved small-molecule inhibitor of angiogenesis, Drugs of today (Barcelona, Spain: 1998); 2006 Jun 1; 42(6):387-98.
    4. Kane RC, Farrell AT, Saber H, Tang S, Williams G, Jee JM, Liang C, Booth B, Chidambaram N, Morse D, Sridhara R. Sorafenib for the treatment of advanced renal cell carcinoma, Clinical Cancer Research; 2006 Dec 15; 12(24):7271-8.
    5. Abdullahi SH, Uzairu A, Ibrahim MT, Umar AB. Chemo-informatics activity prediction, ligand based drug design, Molecular docking and pharmacokinetics studies of some series of 4, 6-diaryl-2-pyrimidinamine derivatives as anti-cancer agents, Bulletin of the National Research Centre; 2021 Dec; 45:1-22.
    6. Liu L, Tang Z, Wu C, Li X, Huang A, Lu X, You Q, Xiang H. Synthesis and biological evaluation of 4, 6-diaryl-2-pyrimidinamine derivatives as anti-breast cancer agents, Bioorganic & Medicinal Chemistry Letters; 2018 Apr 1; 28(6):1138-42.
    7. Stefanachi A, Leonetti F, Pisani L, Catto M, Carotti A. Coumarin: A natural, privileged and versatile scaffold for bioactive compounds; Molecules; 2018 Jan 27; 23(2):250.
    8. Abdullahi SH, Uzairu A, Shallangwa GA, Uba S, Umar AB. In-silico activity prediction, structure-based drug design, molecular docking and pharmacokinetic studies of selected quinazoline derivatives for their antiproliferative activity against triple negative breast cancer (MDA-MB231) cell line, Bulletin of the National Research Centre; 2022 Jan 4; 46(1):2.
    9. Benmansour F, Eydoux C, Querat G, De Lamballerie X, Canard B, Alvarez K, Guillemot JC, Barral K. Novel 2-phenyl-5-[(E)-2-(thiophen-2-yl) ethenyl]-1, 3, 4-oxadiazole and 3-phenyl-5-[(E)-2-(thiophen-2-yl) ethenyl]-1, 2, 4-oxadiazole derivatives as dengue virus inhibitors targeting NS5 polymerase, European journal of medicinal chemistry; 2016 Feb 15; 109:146-56.
    10. Ahmed EY, Latif NA, El-Mansy MF, Elserwy WS, Abdelhafez OM. VEGFR-2 inhibiting effect and molecular modeling of newly synthesized coumarin derivatives as anti-breast cancer agents, Bioorganic & Medicinal Chemistry; 2020 Mar 1; 28(5):115328.
    11. Abdullahi SH, Uzairu A, Shallangwa GA, Uba S, Umar A. Pharmacokinetics studies of some diaryl pyrimidinamine derivatives as anti-cancer agent: in-silico drug design and molecular docking; Advnanced Journal of Chemistry Secton A, 2022; 5(4):320-32.
    12. McTigue M, Murray BW, Chen JH, Deng YL, Solowiej J, Kania RS. Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors, Proceedings of the National Academy of Sciences, 2012 Nov 6; 109(45):18281-9.
    13. Thomsen R, Christensen MH. MolDock: a new technique for high-accuracy molecular docking, Journal of medicinal chemistry; 2006 Jun 1; 49(11):3315-21.
    14. Ibrahim MT, Uzairu A, Shallangwa GA, Uba S. Molecular docking investigation and pharmacokinetic properties prediction of some anilinopyrimidines analogues as egfr t790m tyrosine kinase inhibitors, Egyptian Journal of Basic and Applied Sciences; 2021 Jan 1; 8(1):203-13.
    15. Benhander GM, Abdusalam AA. Identification of potential inhibitors of SARS-CoV-2 main protease from Allium roseum L. molecular docking study, Chemistry Africa; 2022 Feb; 5(1):57-67.
    16. Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: a powerful approach for structure-based drug discovery, Current computer-aided drug design; 2011 Jun 1; 7(2):146-57.
    17. Abdullahi SH, Uzairu A, Shallangwa GA, Uba S, Umar AB. Computational modeling, ligand-based drug design, drug-likeness and ADMET properties studies of series of chromen-2-ones analogues as anti-cancer agents, Bulletin of the National Research Centre; 2022 Dec; 46(1):1-25.
    18. Ugbe FA, Shallangwa GA, Uzairu A, Abdulkadir I. A combined 2-D and 3-D QSAR modeling, molecular docking study, design, and pharmacokinetic profiling of some arylimidamide-azole hybrids as superior L. donovani inhibitors, Bulletin of the National Research Centre; 2022 Dec; 46(1):1-24.
    19. Shaik B, Gupta SP, Zafar T, Anita K. QSAR and Molecular Docking Studies on a Series of 1-Amino-5H-pyrido [4, 3-b] indol-4-carboxamides Acting as Janus Kinase 2 (JAK2) Inhibitors, Letters in Drug Design & Discovery; 2018 Feb 1; 15(2):169-80. 
    20. Šrejber M, Navrátilová V, Paloncýová M, Bazgier V, Berka K, Anzenbacher P, Otyepka M. Membrane-attached mammalian cytochromes P450: An overview of the membrane's effects on structure, drug binding, and interactions with redox partners, Journal of inorganic biochemistry; 2018 Jun 1; 183:117-36.
    21. Smith DA, Beaumont K, Maurer TS, Di L. Clearance in drug design: miniperspective, Journal of Medicinal Chemistry; 2018 Oct 3; 62(5):2245-55. 
    22. Valerio Jr LG. In silico toxicology for the pharmaceutical sciences, Toxicology and applied pharmacology; 2009 Dec 15; 241(3):356-70. 




    Abdullahi Bello Umar,  Sagiru Hamza Abdullahi, Adamu Uzairu, Gideon Adamu Shallangwa, Sani Uba, Molecular Docking Studies of some Coumarin Derivatives as Anti-Breast Cancer agents: Computer-Aided Design and Pharmacokinetics Studies. Prog. Chem. Biochem. Res, 6(3) (2023) 229-243.

    DOI: 10.48309/pcbr.2023.408519.1267