Hadi Adibi, Ehsan Beyhaghi, Sonya Hayati, Leila Hosseinzadeh* and Niloufar Amin* Pages 2439 - 2447 ( 9 )
<p>Background: Isatin (1H-indole-2,3-dione) and its derivatives have been utilized in a variety of biological activities. Anticancer compounds were the most extensively highlighted and explored among the range of beneficial properties. <p> Objective: Herein, we report the targeting effect of halogenated isatin derivatives on cancer cell mitochondria and their antiproliferative mechanism. <p> Methods: A series of novel 5-halo-Isatin derivatives consisting of the 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 <sup>1</sup>H-NMR, FTIR, mass spectroscopy and then tested <i>in vitro</i> 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. <p> Results: The most potent compounds of <b>5b, 5r</b> (IC<sub>50</sub> = 18,13 μM), and <b>5n</b> (IC<sub>50</sub> = 20,17 μM) were found to show strong anticancer activity, especially for MCF7 cells. Further anticancer mechanism studies indicated that <b>5b</b> and <b>5r </b> induced apoptosis through the intrinsic mitochondrial pathway. <p> Conclusion: This research demonstrated that <b>5b</b> and <b>5r </b> have an anticancer property via the modulation of oxidative stress-mediated mitochondrial apoptosis and immune response, which deserves further studies on their clinical applications.</p>
Isatin, 1,3,4-thiadiazole, cytotoxicity, apoptosis, biological activity, antitumor activities.