A metallo pro-drug to target Cu(II) in the context of Alzheimer's disease

International audienceAlzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a Mn(II)-based superoxide dismutase mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target Cu(II) associated events, i.e. Cu(II)-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-beta (Aβ) peptide aggregation. Complex 1+ is able to remove Cu(II) from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity

Copper Conjugates of Nimesulide Schiff Bases Targeting VEGF, COX and Bcl-2 in Pancreatic Cancer Cells

Copper conjugates of Schiff base derivatives of nimesulide (1), a well-known cyclooxygenase-2 (COX-2) inhibitor, were synthesized, structurally characterized and evaluated for their COX selectivity indices and cytotoxicities on pancreatic tumor, BxPC-3 (COX-2 positive) and MiaPaCa (COX-2 negative) cell lines. Copper conjugates exhibit distorted square planar geometries as revealed by the single crystal X-ray structure determination of Cu(L1)2 and show significant growth inhibition in both cell lines (IC50 values 3-26 µM for COX-2 positive and 5-9 µM for COX-2 negative cell line) than the parent nimesulide (35 µM for COX-2 positive and \u3e100 µM for COX-2 negative cell line). The mechanistic pathway for the biological activity involves inhibition of vascular endothelial growth factor (VEGF) and COX inhibition, as well as down regulation of antiapoptotic Bcl-2 and Bcl-XL proteins

Synthesis and characterization of copper(II) complexes of 4-alkyl/aryl-1,2-naphthoquinones thiosemicarbazones derivatives as potent DNA cleaving agents

Copper (II) complexes of some alkyl/aryl-1,2 naphthoquinones thiosemicarbazone have been prepared and characterized. The crystal structure determined for one of the free ligands viz. 4-Pyrrolidine-1-yl-[1, 2] naphthaquinone thiosemicarbazone (5) indicates it to crystallize in the “E’ conformation which is supported by the NMR data. The ligands and copper complexes were evaluated for their DNA cleaving activities in case of circular double stranded plasmid DNA pBR322 under aerobic conditions. Amongst the ligands, compound 8 shows almost quantitative conversion to the linearized DNA in presence of H2O2 oxidant. All copper conjugates show more pronounced interaction with DNA while compounds 3 and 7 are able to yield linearized DNA in presence of the oxidant