Pharmacokinetics Studies of some Diaryl Pyrimidinamine Derivatives as Anti-Cancer Agent: In-Silico Drug Design and Molecular Docking

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-۷ breast cancer cell line and to design novel derivatives with better activities. Compound ۷, with the highest activity (pIC۵۰ = ۵.۳۴۷) and low residual value (۰.۰۱۳), was embraced as the design template. Compared to the template, the designed compounds revealed better activities ranging from pIC۵۰ = ۶.۰۶ to ۷.۱۴. The results of molecular docking studies demonstrated that the designed compounds exhibit higher binding affinities ranging from -۱۵۵.۹ to -۱۸۱.۴ cal/mol compared to the control drug: Tamoxifen (-۱۵۵.۲ 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. 

Keywords:

Estrogen Receptor , QSAR model , Molecular docking , Pharmacokinetic studies , In-silico drug design , breast cancer