Pharmacokinetics Studies of some Diaryl Pyrimidinamine Derivatives as Anti-Cancer Agent: In-Silico Drug Design and Molecular Docking
نویسندگان
1 Department of Chemistry, Faculty of Physical Sciences, Ahmadu Bello University, P.M.B.1045, Zaria, Kaduna State, Nigeria
2 Department of Chemistry, Faculty of Physical Sciences, Ahmadu Bello University, P.M.B.1045, Zaria, Kaduna State, Nigeria
3 Department of Chemistry, Faculty of Physical Sciences, Ahmadu Bello University, P.M.B.1045, Zaria, Kaduna State, Nigeria
4 Department of Chemistry, Faculty of Physical Sciences, Ahmadu Bello University, P.M.B.1045, Zaria, Kaduna State, Nigeria
5 Department of Chemistry, Faculty of Physical Sciences, Ahmadu Bello University, P.M.B.1045, Zaria, Kaduna State, Nigeria
doi
10.22034/ajca.2022.357747.1325چکیده
The cost and duration of novel drug discovery and synthesis have been the significant drawbacks to the chemotherapeutic treatment of breast cancer. To combat these challenges, a validated QSAR model was developed to predict the inhibitive capacities of diaryl-pyridinamine analogs against the MCF-7 breast cancer cell line and to design novel derivatives with better activities. Compound 7, with the highest activity (pIC50 = 5.347) and low residual value (0.013), was embraced as the design template. Compared to the template, the designed compounds revealed better activities ranging from pIC50 = 6.06 to 7.14. The results of molecular docking studies demonstrated that the designed compounds exhibit higher binding affinities ranging from -155.9 to -181.4 cal/mol compared to the control drug: Tamoxifen (-155.2 cal/mol). The designed compounds exhibit drug-likeness and promising ADMET properties, as revealed from pharmacokinetics studies. Therefore, the aftermaths of this research could be significant in discovering new and improved anti-breast cancer agents.
