Cytotoxic activities of the pyrimidine-based acetamide and isophthalimide derivatives: an in vitro and in silico studies

ABSTRACT

In here, a series of pyrimidin-(1(2H)-yl)acetamide and pyrimidin-(1(2H)-yl)isophthalimide derivatives were synthesised according to literature. The cytotoxic activity properties of these molecules were screened against human cancer cell lines as in vitro. The results demonstrated that these molecules had moderate effects on cancer cell lines for 48 h. The binding potential of the relatively active compound, ZF1, towards CDK1 (cyclin-dependent kinase 1) was investigated through molecular docking. The stability of the enzyme-ZF1 complex procured from the molecular docking was assessed through molecular dynamics (MD) simulation. Then, the electrochemical properties of the synthesised compounds were computed through density functional theory (DFT) studies. Computational pharmacokinetic analysis was also performed. The computational studies revealed that ZF1 could bind to CDK1 but its binding potential was less than the standard drug. The MD simulation exhibited that the compound could be stable inside the binding region during the simulation period. ZP3 is predicted to have the highest chemical stability among the synthesised compounds. Furthermore, the computational pharmacokinetic study revealed that ZP1, ZP2, and ZP3 had drug-like properties.

KEYWORDS:

• Cytotoxic activity
• docking
• DFT
• MD simulation

Acknowledgements

M.T.M. did the molecular docking, MD simulations, and DFT studies. Z.K. synthesised molecules. S.A. designed the study, did cytotoxic activity studies, and wrote the paper.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Süleyman Demirel University with project number TSG-2021-8458.