<p>A novel series of 1,3-thiazin-4-one derivatives containing a piperidyl ring (<b>7</b>–<b>16</b>) were designed and synthesized efficiently by thioamide and acetylene diester cyclization reaction <i>via</i> aminolysis of the ester group and the elimination of an alcohol molecule. The structures of all the novel compounds were established by their FTIR, Mass, <sup>1</sup>H NMR, and <sup>13</sup>C NMR spectral techniques. The newly synthesized compounds (<b>7</b>–<b>16</b>) were studied for their <i>in vitro</i> anticancer activity against human liver cancer cell lines Hep G2 using MTT assay. The IC<sub>50</sub> values of the tested compounds were ranging in between 7.48 ± 0.71 and 56.57 ± 1.37 µM. Further, the apoptosis evaluation by the mitochondrial membrane potential using JC-1 dye was carried out and the results are in good agreement with the cytotoxicity studies.</p
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