Intramolecular Ring Transformation of Bis-oxadiazoles to Bis-thiadiazoles and Investigation of Their Anticancer Activities

A new series of 2,6-dimethyl-4-phenyl-N3,N5-bis(3-phenyl-1,3,4-thiadiazol-2(3H)-ylidene)-1,4-dihydropyridine-3,5-dicarbohydrazides were synthesized from reaction of 5,5-(2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-diyl)bis(1,3,4-oxadiazole-2-thiol) or diethyl 2,2-(2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarbonyl)bis(hydrazine-1-carbodithioate) with various hydrazonoyl chlorides. The structures of new compounds were established on the basis of their elemental analysis and IR, H-1 NMR, and mass spectral data. The anticancer activities of the synthesized compounds were screened for their activity against human hepatocellular carcinoma (HepG2) cell lines, and the results showed that compounds 6l, 6k, and 6e were the most active (IC50=7.68 +/- 9.8, 8.72 +/- 9.7, and 9.78 +/- 9.1M, respectively), compared with Cisplatin reference drug (IC50 value of 1.40 +/- 1.1M).