803712-70-1Relevant articles and documents
Synthetic prodiginine obatoclax (GX15-070) and related analogues: Anion binding, transmembrane transport, and cytotoxicity properties
Diaz De Grenu, Borja,Hernandez, Paulina Iglesias,Espona, Margarita,Quinonero, David,Light, Mark E.,Torroba, Tomas,Perez-Tomas, Ricardo,Quesada, Roberto
, p. 14074 - 14083 (2011)
Synthetic prodiginine obatoclax shows promise as a potential anticancer drug. This compound promotes apoptosis of cancer cells, although the mechanism of action is unclear. To date, only the inhibition of BCL-2 proteins has been proposed as a mechanism of action. To gain insight into other possible modes of action, we have studied the anion-binding properties of obatoclax and related analogues in solution, in the solid state, and by means of density functional theory calculations. These compounds are well suited to interact with anions such as chloride and bicarbonate. The anion-transport properties of the compounds synthesized were assayed in model phospholipid liposomes by using a chloride-selective-electrode technique and 13C NMR spectroscopy. The results demonstrated that these compounds are efficient anion exchangers that promote chloride, bicarbonate, and nitrate transport through lipid bilayers at very low concentrations. In vitro studies on small-cell lung carcinoma cell line GLC4 showed that active ionophores are able to discharge pH gradients in living cells and the cytotoxicity of these compounds correlates well with ionophoric activity.
Synthesis and biological activity of obatoclax derivatives as novel and potent SHP-1 agonists
Su, Jung-Chen,Chen, Wei-Lin,Liu, Chun-Yu,Shiau, Chung-Wai,Chen, Kuen-Feng,Chen, Pei-Jer,Tai, Wei-Tien,Huang, Jui-Wen,Kim, Inki
, p. 127 - 133,7 (2012/12/12)
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.
Chemoenzymatic synthesis of prodigiosin analogues - Exploring the substrate specificity of PigC
Chawrai, Suresh R.,Williamson, Neil R.,Salmond, George P. C.,Leeper, Finian J.
, p. 1862 - 1864 (2008/12/22)
Analogues of prodigiosin, a tripyrrolic pigment produced by Serratia species with potent immunosuppressive and anticancer activities, have been produced by feeding synthetic analogues of the normal precursor MBC to mutants of Serratia sp. ATCC 39006 or to engineered strains of Escherichia coli; in this way it has been shown that the prodigiosin synthesising enzyme, PigC, has a relaxed substrate-specificity. The Royal Society of Chemistry.