A gliclazide complex based on palladium towards Alzheimer's disease: promising protective activity against A beta-induced toxicity in C. elegans
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AuthorGarcía García, Amalia; Rojas Macías, Sara; Rivas García, Lorenzo; Navarro Hortal, María Dolores; Romero Márquez, José Manuel; Choquesillo Lazarte, Duane; Salinas Castillo, Alfonso; Quiles Morales, José Luis; Rodríguez Diéguez, Antonio
Royal Society of Chemistry
Chem. Commun., 2022, Advance Article. DOI: [10.1039/d1cc04404d]
SponsorshipSpanish Government PGC2018-102052-B-C21 PID2020-116460RB-I00; Junta de Andalucia FQM-394 FQM-134; FEDER/Junta de Andaluci'a Consejeri'a de Economi'a y Conocimiento B-AGR-193-UGR18; MCIN/AEI/ PID2020-116460RB-I00; Juan de la Cierva Fellowship IJC2019-038894-I
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 A beta-induced toxicity in the Caenorhabditis elegans model, which has never been reported.