ONO‐Pincer‐Type Coumarin‐Based Copper(II) Metalates: Effect on Alzheimer's Disease Pathologies in Caenorhabditis elegans

Four copper(II) complexes 1–4 of 3‐acetylchromene‐2‐one and substituted 3‐acetylchromene‐2‐one derived Schiff bases were synthesized and structurally characterized using analytical and spectral techniques. The molecular structure of complex 1 has been confirmed by single crystal X‐ray diffraction studies, which revealed that ligand 3‐acetylchromene‐2‐one‐4 N‐semicarbazone is coordinated to the metal as ONO pincer type ligand. Two nitrate molecules are coordinated to the copper ion through oxygen atoms, of which one nitrate molecule was found to coordinate via two oxygen atoms, thereby achieving six‐coordination. Preliminary biological studies like DNA and protein binding analyses indicated the binding of the ligands and complexes to CT‐DNA (Calf Thymus DNA) and BSA (Bovine Serum Albumin). We investigated the effects of complexes 1–4 against amyloid‐β (Aβ) toxicity using transgenic Caenorhabditis elegans strains expressing muscle‐ and neuronal‐specific human Aβ1‐42. The results showed that the complexes 2–4 remarkably reduced the Aβ‐induced paralysis phenotype, Aβ plaque deposition, and other Alzheimer's disease‐associated functional deficits in C. elegans by their potent antioxidant and anti‐aggregative properties. Complexes 2–4 delayed Alzheimer's disease pathologies, providing a basis for further investigating these effects on higher models. The presented work describes the synthesis of four water soluble Cu(II) complexes containing coumarin Schiff base ligands. They were structurally characterized, and their DNA and protein binding affinities were analyzed. Using C. elegans as a model, the effect of the complexes against Aβ toxicity was studied, and it was shown that complexes 2–4 delay Alzheimer's disease pathologies.