Title:In Vitro Cytotoxicity and Apoptosis Inducing Evaluation of Novel Halogenated Isatin
Derivatives
Volume: 22
Issue: 13
Author(s): Hadi Adibi, Ehsan Beyhaghi, Sonya Hayati, Leila Hosseinzadeh*Niloufar Amin*
Affiliation:
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Keywords:
Isatin, 1, 3, 4-thiadiazole, cytotoxicity, apoptosis, biological activity, antitumor activities.
Abstract:
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.
Objective: Herein, we report the targeting effect of halogenated isatin derivatives on cancer cell mitochondria and their
antiproliferative mechanism.
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 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.