Design and evaluation of ester-containing PEPPSI Type Pd(II)NHC complexes as multitarget enzyme inhibitors

Abstract

This work reports the synthesis and characterization of a series of PEPPSI-type (NHC)PdBr2(Py) complexes bearing ester-functionalized N-heterocyclic carbene (NHC) ligands. The complexes were characterized using 1H and 13C NMR, FTIR spectroscopy, and X-ray crystallography. Single-crystal X-ray diffraction confirmed the square-planar geometry around the Pd(II) center. The synthesized complexes demonstrated significant inhibitory ability against alpha-glycosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), with Ki values ranging from 17.63 +/- 2.65 to 106.13 +/- 3.78 nM. Molecular docking studies revealed key interactions between the complexes and the active sites of the target enzymes, providing insights into their inhibitory mechanisms. Notably, complexes 1f, 1i, and 1e exhibited the highest potency, suggesting their potential as therapeutic agents for metabolic and neurodegenerative disorders.