Synergistic Insights: Synthesis, Characterization, Biological Evaluation, and Molecular Docking Studies of TMS-N3 UGI–Adduct

In the context of ongoing research, an efficient single-step multicomponent reaction synthesis for new tetrazole scaffolds has been developed. The Ugi multicomponent process is one of the most promising approaches for the connection of four separate components in a single phase and finds immense application in drug discovery. In this study, tetrazoles were synthesized using the Ugi-Multi Component technique, which involved the condensation of isocyanides, TMS-N₃, different aryl amines, aromatic aldehydes with active pharmacophores. Final products were characterized by various spectroscopic techniques viz. IR, NMR, and Mass spectrometry. Tetrazole derivatives were screened for their anticancer activity against the NCI-60 cell lines grouped in 9 different subpanels among which compounds 5b and 5e have been found to be more potent against different cell lines. In order to get mechanistic insights into this antitumor activity, molecular docking analysis against critical target CDK2 was performed. The results of binding affinity were in harmony with the anticancer activity and could provide valuable insights into the various thermodynamic interactions governing the binding affinity.