Objectives: One of the best targets for anticancer medication is human dihydrofolate reductase (hDHFR), as it is crucial to produce purines and pyrimidines. Moreover, it keeps the biological folate pools inside the cells. Due to certain similarities to folic acid, quinazolinone-based thiazolidine chemicals are more well-known and have offered appealing scaffolding for developing anticancer medicines. To assess the potential for various quinazolinyl thiazolidine scaffolds as inhibitors of the human dihydrofolate reductase enzyme, molecular docking and in-silico investigations were conducted in this work.

Methods: Ten compounds from the class of quinazolinones and the common medication methotrexate were included in the investigation. The PyRx suite was used to perform automated molecular docking of compounds based on thiazolidine quinazolinone with human DHFR. Molinspiration made predictions about the features of molecular descriptors.

Results: As shown by the findings of the molecular docking, all of the derivatives met Lipinski's rule of five and occupied the same cavity in the protein molecule as the synthetic medication methotrexate and the natural ligand folic acid. In comparison to methotrexate, all the chemical complex's binding energies have significantly lower values.

Conclusion: According to the molecular docking investigation, the chemicals may function as a possible substitute for hDHFR. The created pharmacophore may also be utilised to create and develop novel medications. This work provides strong evidence in favour of the hypothesis that these chemicals are potential human DHFR inhibitors.

Keywords: Quinazolinone based thiazolidines, Lipinski’s rule, molecular docking, ADME, human DHFR inhibitors as anticancer agents.