A gliclazide complex based on palladium towards Alzheimer's disease: promising protective activity against Aβ-induced toxicity in C. elegans
2022
García-García, Amalia | Rojas Macias, Sara | Rivas-García, Lorenzo | Navarro-Hortal, María D. | Romero-Márquez, Jose M. | Fernández-Bolaños, José G. | Choquesillo-Lazarte, Duane | Salinas-Castillo, Alfonso | López, Oscar | Quiles, José L. | Rodríguez Dieguez, Antonio
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.
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