An Efficient Synthesis of Novel Aminothiazolylacetamido-Substituted 3,5-Bis(arylidene)-4-piperidone Derivatives and Their Cytotoxicity Studies.

The expansion of 3,5-bis(arylidene)-4-piperidone derivatives with heterocyclic compounds such as 1,3-thiazole should take into account this correlation. The synthesized aminothiazolylacetamido-substituted 3,5-bis(arylidene)-4-piperidone derivatives - were found to have GI values in the range of 0.15-0.28 μM against HeLa and HCT116 cancer cell lines. docking studies confirmed that the proteasome inhibition mechanism involves a nucleophilic attack from the N-terminal threonine residue of the β-subunits to the C=O group of compounds. A C=O group of amide was able to interact with the NH group of the alanine residue and the NH group of amino thiazole, along with an OH group of the serine residue. These results strongly suggest that the synthesized compounds could be a potential candidate inhibitor of the 20S proteasome. These molecules have the potential to be developed as cytotoxic and anticancer agents, as revealed by this study.