Molecular docking studies of some coumarin derivatives as anti-breast cancer agents: Computer-aided design and pharmacokinetics studies
نویسندگان
1 Department of chemistry, Faculty of physical sciences, Ahmadu Bello University, Zaria, Kaduna, Nigeria
2 Department of chemistry, Faculty of physical sciences, Ahmadu Bello University, Zaria, Kaduna, Nigeria
3 Department of chemistry, Faculty of physical sciences, Ahmadu Bello University, Zaria, Kaduna, Nigeria
4 Department of chemistry, Faculty of physical sciences, Ahmadu Bello University, Zaria, Kaduna, Nigeria
5 Department of chemistry, Faculty of physical sciences, Ahmadu Bello University, Zaria, Kaduna, Nigeria
doi
10.48309/pcbr.2023.398753.1265چکیده
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.
