Synthesis, structure prediction, pharmacokinetic properties, molecular docking and antitumor activities of some novel thiazinone derivatives

A novel series of thiazinone derivatives were obtained from unexpected cyclization of dimethyl acetylenedicarboxylate (DMAD) and diethyl acetylenedicarboxylate (DEAD) with corresponding 3-alkyl-2,6-diarylpiperidin-4-one thiosemicarbazones in dry methanol without catalyst under mild conditions. The structures of newly synthesized compounds were established on the basis of FT-IR, HR-Mass, 1 H-NMR, 13 C-NMR, 1 H- 1 H COSY, 1 H- 13 C COSY, DEPT-135, and HMBC spectral techniques. From 1 H NMR, all newly synthesized compounds 17–24 were found to adopt chair conformation. The theoretical studies were carried out using Schrödinger software suite for the structure prediction, biochemical properties investigation and docking studies of all novel compounds. To study the antitumor activity, all the novel compounds were screened in vitro for their cytotoxicity and apoptosis activity against Hep G2 human liver cancer cell line. The biological analysis revealed that the newly synthesized compounds have good/moderate inhibitory activity against the tested cell line.