Affiliation:
1. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
2. Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
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.
Method:
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.
Funder
Vice Chancellery for Research and Technology, Kermanshah University of Medical Sciences
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Cited by
3 articles.
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