A gliclazide complex based on palladium towards Alzheimer's disease: promising protective activity against Aβ-induced toxicity in C. elegans

Amalia García-García; Sara Rojas; Lorenzo Rivas-García; María D. Navarro-Hortal; Jose M. Romero-Márquez; José G. Fernández-Bolaños; Duane Choquesillo-Lazarte; Alfonso Salinas-Castillo; Óscar López; José L. Quiles; Antonio Rodríguez-Diéguez

Resumen:

A new palladium coordination compound based on gliclazide with the chemical formula [Pd(glz)2] (where glz = gliclazide) has been synthesized and characterised. The structural characterization reveals that this material consists of mononuclear units formed by a Pd2+ ion coordinated to two molecules of the glz ligand, in which palladium ions exhibit a distorted plane-square coordination sphere. This novel material behaves like a good and selective inhibitor of butyrylcholinesterase, one of the most relevant therapeutic targets against Alzheimer's disease. Analysis of the enzyme kinetics showed a mixed mode of inhibition, the title compound being capable of interacting with both the free enzyme and the enzyme-substrate complex. Finally, the palladium compound shows promising protective activity against Aβ-induced toxicity in the Caenorhabditis elegans model, which has never been reported.