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

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

  • ACS Omega. 2024 Jun 26;9(27):29244-29251. doi: 10.1021/acsomega.4c00039.
Thangaiyan Suresh 1,  Dhatchana Moorthy Nachiappan 2,  G Karthikeyan 3,  Vijayaparthasarathi Vijayakumar 1,  Jerry P Jasinski 4,  Sundaramoorthy Sarveswari 1
Affiliations

Affiliations

  • 1 Department of Chemistry, School of Advanced Sciences, VIT University, Vellore 632014, Tamil Nadu, India.
  • 2 Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India.
  • 3 Amity Institute of Virology and Immunology, Amity University, Noida 201303, Uttar Pradesh, India.
  • 4 Keene State College, 229 Main Street, Keene, New Hampshire 03435-200, United States.
PMID: 39005779 DOI: 10.1021/acsomega.4c00039
Abstract

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 3a-j were found to have GI50 values in the range of 0.15-0.28 μM against HeLa and HCT116 Cancer cell lines. In silico 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 5g 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.

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