Abstract:
A new series of 5-(4-chlorophenyl)-1,3,4-thiadiazole-based compounds featuring pyri-
dinium (3), substituted piperazines (4a–g), benzyl piperidine (4i), and aryl aminothiazoles (5a–e)
heterocycles were synthesized. Evaluation of the cytotoxicity potential of the new compounds against
MCF-7 and HepG2 cancer cell lines indicated that compounds 4e and 4i displayed the highest activity
toward the tested cancer cells. A selectivity study demonstrated the high selective cytotoxicity of
4e and 4i towards cancerous cells over normal mammalian Vero cells. Cell cycle analysis revealed
that treatment with either compound 4e or 4i induced cell cycle arrest at the S and G2/M phases in
HepG2 and MCF-7 cells, respectively. Moreover, the significant increase in the Bax/Bcl-2 ratio and
caspase 9 levels in HepG2 and MCF-7 cells treated with either 4e or 4i indicated that their cytotoxic
effect is attributed to the ability to induce apoptotic cell death. Finally, an in vivo radioactive tracing
study of compound 4i proved its targeting ability to sarcoma cells in a tumor-bearing mice model.
