Investigating the Activity of Indole-2-on Derivative Src Kinase Inhibitors Against Chronic Myeloid Leukemia Cells

Author(s):

Aysegul Cort-Donmez, Sureyya Olgen*, Ersin Guner, Gulsum Akgun-Cagliyan, Ferhat Hanikoglu, Melek Tunc-Ata and Emine Kilic-Toprak   Pages 113 - 122 ( 10 )

Abstract:

<p>Background: Src family tyrosine kinases play a potential role in Bcr-Abl-induced leukemogenesis. Src kinase inhibitors are reported as selective inhibitors of chronic myeloid leukemia. <p> Objective: Since Src kinase inhibitors have an inhibitive effect on chronic myeloid leukemia, indole derivatives (C-1, C-2, C-3) previously found as potent inhibitors of Src kinase were tested against chronic myeloid leukemia in this study. <p> Methods: Cell viability of K562 and R/K562 cells, antiproliferative and antioxidant effects, and inhibition profiles of Bcr-Abl kinase of indole derivatives were determined compared to dasatinib and imatinib. <p> Results: The results showed that compounds affected cell proliferation and decreased the levels of Bcr/Abl. These results confirmed that the antileukemic activity of compounds was related to Bcr/Abl expression. Docking studies also presented that compounds are inhibitors of both Src and Abl kinases. Calculation of drug-like properties showed that compounds could be potential drug candidates. <p> Conclusion: Among indole-2-on derivatives, previously identified as Src kinase inhibitors, C-2 has been discovered to be a strong anticancer drug that is active against susceptible and resistant K562 cell lines and induces apoptosis.</p>

Keywords:

Indole-2-on derivatives, anti-proliferative, cell viability, Src, ABl, docking.

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