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Abstract:Reactions of ethylidenethiocarbohydrazide with hydrazonoyl halides gave 1,3-thiazole or 1,3,4-thiadiazole derivatives according to the type of hydrazonoyl halides. Treatment of ethylidenethiosemicarbazide with hydrazonoyl halides and dimethylacetylene dicarboxylate (DMAD) afforded the corresponding arylazothiazoles and 1,3-thiazolidin-4-one derivatives, respectively. The structures of the synthesized products were confirmed by IR, 1 H-NMR, 13 C-NMR and mass spectral techniques. The cytotoxic activity of the selected products against the Hepatic carcinoma cell line (Hepg-2) was determined by MTT assay indicating a concentration dependent cellular growth inhibitory effect, especially for compounds 14c and 14e. The dose response curves indicated the IC 50 (the concentration of test compounds required to kill 50% of cell population) were 0.54 µM and 0.50 µM, respectively. Confocal laser scanning imaging of the treated cells stained by Rhodamin 123 and Acridine orange dyes confirmed that the selected compounds inhibit the mitochondrial lactate dehydrogenase enzymes. The binding mode of the active compounds was interpreted by a molecular docking study. The obtained results revealed promising cytotoxic activity.

The reaction of one equivalents of 5‐acetylthiadiazole with one equivalent of aldehyde in acetic acid and ammonium acetate yielded thiadiazolyl‐pyridine derivatives in a multicomponent reactions. The structures of all the new compounds were elucidated on the basis of elemental analysis and spectral data. The anticancer activities of the synthesized compounds were screened for their activity against human lung carcinoma (A549) and human hepatocellular carcinoma cell lines (HepG2) comparable with cisplatin, and the results showed that most of such compounds exhibit considerable activities. The order of activity against A549 cell line was 4c, 4e, 4a, 6d, 8d, 11, 12, 4b, 4f, and 4d. However, compound 4e exhibited the highest activity against HepG2, followed by 4a, 4c, 6d, 8d, 11, 12, 4f, 4d, and 4b. On the other hand, compounds 11, 12, and 4b showed the highest 2,2‐diphenyl‐1‐picrylhydrazyl free radical scavenging activities. Conclusively, the results of the current study approved the cytotoxic and antioxidant capabilities of the synthesized compounds.

The reaction of 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarbohydrazide with variety of carbonyl compounds such as substituted benzaldehydes, cycloalkanones and hetero-cyclic ketones under grinding method under catalyst-and solvent-free conditions at room temperature, in the presence of catalytic drops of acetic acid gave a new series of 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarbohydrazone derivatives in good to excellent yields. The structures of new products were elucidated on the basis of their spectral data and elemental analysis. Most of the newly prepared compounds were evaluated towards HepG2 cell lines and showed good IC 50 for some compounds. Additionally, molecular docking of the novel chemical entities using Autodock Vina demonstrated their binding modes within the active site of DYRK1A.