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

A new series of 2,6‐dimethyl‐4‐phenyl‐ N ′3, N ′5‐bis(3‐phenyl‐1,3,4‐thiadiazol‐2(3 H )‐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, 1 H 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 (IC 50  = 7.68 ± 9.8, 8.72 ± 9.7, and 9.78 ± 9.1 μM, respectively), compared with Cisplatin reference drug (IC 50 value of 1.40 ± 1.1 μM).