Synthesis and bioactivity of N-glycosylated 3-(2-oxo-2-arylethylidene)-indolin-2-ones

Abstract

N-Glycosyl-3-alkylideneoxindoles, N-glycosylated 3-(2-oxo-2-arylethylidene)indolin-2-ones, were prepared by reaction of isatin-N-glycosides with substituted acetophenones.

Crucial role of reactive oxygen species (ROS) for the proapoptotic effects of indirubin derivative DKP‐073 in melanoma cells

“…This previously used derivative was further modified by the integration of a fluoride residue resulting in DKP‐073 (Figure A). In A‐375 melanoma cells, it resulted in loss of cell viability and reduced cell proliferation . Here, we demonstrate significant apoptosis induction by DKP‐073 in three representative melanoma cell lines, which was further enhanced by the combination with TRAIL.…”

“…For induction of apoptosis, cells were treated with KillerTRAIL™ (Adipogen, San Diego, CA, AG‐40T‐0001; 20 ng/mL) and the indirubin derivate DKP‐073 (10 μM), whereas control cells received only the solvent DMSO. The chemical structure of DKP‐073 (substance 9e) as well as reduced cell viability and cell proliferation in A‐375 at 24 h had been previously reported …”

“…The chemical structure of DKP-073 (substance 9e) as well as reduced cell viability and cell proliferation in A-375 at 24 h had been previously reported. 21 For inhibition of apoptosis, cells were pretreated for 1 h, before agonists were applied, with the pan-caspase inhibitor QVD-OPh (Abcam, Cambridge, UK; 10 μM), the antioxydative agent N-Acetylcystein (Sigma-Aldrich, Taufkirchen, Germany; 800 μM) or the NOX inhibitors Ebselen (Cay-70530, 50 μM; Cayman Chemical, Ann Arbor, MI), and GKT-137831 (50-100 μM; Selleckchem, Munich, Germany).…”

“…The series of stepwise modifications performed in our lab enclosed the introduction of a sugar residue at position 1, followed by deletion of the secondary amino group at position 1′ and substitution at position 6′ by a methoxy group . In the so far final step, the methoxy group was substituted by chemically active groups as a fluoride in case of DKP‐073 …”

“…19,20 In the so far final step, the methoxy group was substituted by chemically active groups as a fluoride in case of DKP-073. 21 Here, we investigated the proapoptotic effects of DKP-073 in melanoma cells in more detail and unraveled the downstream signaling pathways, which appeared as essentially based on the production of reactive oxygen species. This opens new perceptions in the proapoptotic targeting of melanoma.…”