15 research outputs found
The novel arylindolylmaleimide PDA-66 displays pronounced antiproliferative effects in acute lymphoblastic leukemia cells
Background: Prognosis of adult patients suffering from acute lymphoblastic leukemia (ALL) is still unsatisfactory. Targeted therapy via inhibition of deregulated signaling pathways appears to be a promising therapeutic option for the treatment of ALL. Herein, we evaluated the influence of a novel arylindolylmaleimide (PDA-66), a potential GSK3ÎČ inhibitor, on several ALL cell lines.Methods: ALL cell lines (SEM, RS4;11, Jurkat and MOLT4) were exposed to different concentrations of PDA-66. Subsequently, proliferation, metabolic activity, apoptosis and necrosis, cell cycle distribution and protein expression of Wnt and PI3K/Akt signaling pathways were analyzed at different time points.Results: PDA-66 inhibited the proliferation of ALL cells significantly by reduction of metabolic activity. The 72 h IC50 values ranged between 0.41 to 1.28 ÎŒM PDA-66. Additionally, caspase activated induction of apoptosis could be detected in the analyzed cell lines. PDA-66 influenced the cell cycle distribution of ALL cell lines differently. While RS4;11 and MOLT4 cells were found to be arrested in G2 phase, SEM cells showed an increased cell cycle in G0/1 phase.Conclusion: PDA-66 displays significant antileukemic activity in ALL cells and classifies as candidate for further evaluation as a potential drug in targeted therapy of ALL
The novel arylindolylmaleimide PDA-66 displays pronounced antiproliferative effects in acute lymphoblastic leukemia cells
Synthesis of 1-((4-methoxyphenyl)-3-alkynes)-1 H -pyrrole-2,5-diones and functionalization to triazoles
From Propargylamides to Oxazole Derivatives: NIS-Mediated Cyclization and Further Oxidation by Dioxygen
1,3-Dipolar cycloaddition reaction of indoles with tosyl azide, subsequent dehydroaromatization and ring-opening cascade: a computational study
Synthesis of Pharmacologically Relevant New Derivatives of Maleimides via Ligand-Free Pd-Catalyzed SuzukiâMiyaura Cross-Coupling Reactions
Preparation of tetrasubstituted 3-phosphonopyrroles through hydroamination: scope and limitations
Phosphonylated pyrroles were obtained by a ZnCl2-catalyzed 5-exo-dig hydroamination of propargylic enamines. These starting compounds were obtained in two steps from commercially available beta-ketophosphonates. The method tolerates a wide variety of substituents at the 1,2- and 5-position of the pyrrole, while further derivatization allows for the introduction of substituents at the 4-position via lithiation or halogenation