Introduction: Lung cancer is presumed to be the most notable cause of morbidity and impermanency
in human beings caused by uncontrolled cell proliferation of lung tissue which results in
abrupt synthesis of DNA.
Methods: Prevention of DNA synthesis can show distinctive effect on lung cancer by utilizing Thymidylate
synthase (TS), a key rate-limiting enzyme in the DNA synthesis process. However, the
available finite aggregate of clinically approved blockers and their corresponding side effects lead
to the urgent origination of novel inhibitors.
Results and Discussion: In silico approaches (QSAR and molecular docking) have been accomplished
to discover new potential inhibitors of TS providing a new strategy to evolve novel thymidylate
synthase inhibitors functional in lung cancer.
Conclusion: In the present study chemical features of a series of compounds alongside their activities
alternating over numerous orders of magnitudes was utilized to generate QSAR models, and these
could be further employed to predict the activity of new designed compounds. 3D‒QSAR kNNSW
based model with decent statistical data having q2 approximately 95% (internal validation) and
80% (external validation) has validated the importance of steric feature. Further docking analysis using
D‒score and ligand receptor interactions indicated that all the studied compounds are well accommodated
in the binding pocket of TS and disparities in the activity are controlled by hydrogen
and hydrophobic interactions.