Synthesis and biological activity of obatoclax derivatives as novel and potent SHP-1 agonists
Journal
European Journal of Medicinal Chemistry
Journal Volume
56
Pages
127-133
Date Issued
2012
Author(s)
Abstract
Obatoclax is a linear oligopyrrole compound which antagonizes the antiapoptotic effects of the Bcl-2 family. Herein we describe the synthesis of obatoclax derivatives by replacement of the pyrrole and indole ring of obatoclax with thiophene, furan and thiazolidinedione. The in vitro cytotoxicity of the newly synthesized compounds is evaluated against hepatocellular carcinoma cells. Pyrrole and indole substituents of obatoclax analogues exhibited potent inhibition of cell growth. Among the tested compounds, 5d and 5e were active at 6.3 and 13.2 μM against PLC5 cells. Further assays confirmed a correlation between cell death, and p-STAT3 inhibition and SHP-1 activation by these analogues. ? 2012 Elsevier Masson SAS. All rights reserved.
Subjects
Cytotoxicity; Obatoclax; SHP-1; STAT3
SDGs
Other Subjects
2 [2 [(1h pyrrol 2 yl)methylene] 3 methoxy 2h pyrrol 5 yl] 1h indol; 2 [2 [(1h pyrrol 2 yl)methylene] 3 methoxy 2h pyrrol 5 yl] 5 bromo 1h indol; 2,4 thiazolidinedione; antineoplastic agent; furan; indole; obatoclax; obatoclax derivative; protein tyrosine phosphatase SHP 1; pyrrole; STAT3 protein; thiophene; unclassified drug; article; biological activity; cancer cell; concentration response; controlled study; correlation coefficient; cytotoxicity; drug activity; drug potency; drug synthesis; enzyme activation; human; human tissue; in vitro study; liver cell carcinoma
Publisher
Elsevier Masson SAS
Type
journal article