LAUSR

BACKGROUND Isatin (1H-indole-2,3-dione) and its derivatives have been shown their responsibility in a wide range of biological activities. Among the range of beneficial properties, anticancer compounds were the most extensively highlighted and explored. OBJECTIVE Herein, we report the targeting effect of halogenated isatin derivatives on cancer cell mitochondria and their antiproliferative mechanism. METHOD A series of novel 5-halo-Isatin derivatives consisting 5-Amino-1,3,4-thiadiazole-2-thiol scaffold were synthesized and easily conducted in good yields through a condensation reaction between keto groups of Isatin and primary amine under alcoholic conditions, followed by S-benzylation. The compounds were fully characterized using spectroscopic methods such as 1H-NMR, FTIR, mass spectroscopy and then tested in vitro towards three cancer cell lines HT-29 (colon cancer), MCF-7 (breast cancer) and SKNMC (neuroblastoma). Apoptosis induction was investigated through assessment of caspase 3 and mitochondrial membrane potential. RESULTS The most potent compounds of 5b, 5r (IC50 = 18,13 µM) and 5n (IC50 = 20,17 µM) were found to show strong anticancer activity, especially for MCF7 cells. Further anticancer mechanism studies indicated that 5b and 5r induced apoptosis through the intrinsic mitochondrial pathway. CONCLUSION This research demonstrated that 5b and 5r have an anticancer property via the modulation of oxidative stress-mediated mitochondrial apoptosis and immune response, which deserves further studies on their clinical applications.