Suresh Thangaiyan, Nachiappan Dhatchana Moorthy, Karthikeyan G, Vijayakumar Vijayaparthasarathi, P Jasinski Jerry, Sarveswari Sundaramoorthy
Department of Chemistry, School of Advanced Sciences, VIT University, Vellore 632014, Tamil Nadu, India.
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India.
ACS Omega. 2024 Jun 26;9(27):29244-29251. doi: 10.1021/acsomega.4c00039. eCollection 2024 Jul 9.
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.
3,5-双（亚芳基）-4-哌啶酮衍生物与杂环化合物（如1,3-噻唑）的扩环反应应考虑到这种相关性。合成的氨基噻唑基乙酰氨基取代的3,5-双（亚芳基）-4-哌啶酮衍生物——对HeLa和HCT116癌细胞系的GI值在0.15 - 0.28 μM范围内。对接研究证实，蛋白酶体抑制机制涉及β亚基N端苏氨酸残基对化合物C=O基团的亲核攻击。酰胺的C=O基团能够与丙氨酸残基的NH基团、氨基噻唑的NH基团以及丝氨酸残基的OH基团相互作用。这些结果有力地表明，合成的化合物可能是20S蛋白酶体的潜在候选抑制剂。这项研究表明，这些分子有潜力被开发为细胞毒性和抗癌剂。
