TY - JOUR
T1 - Grid-Type Quaternary Metallosupramolecular Compounds Inhibit Human Cholinesterases through Dynamic Multivalent Interactions
AU - Nachon, Florian
AU - Brazzolotto, Xavier
AU - Dias, José
AU - Courageux, Charlotte
AU - Drożdż, Wojciech
AU - Cao, Xiao-Yu
AU - Stefankiewicz, Artur R.
AU - Lehn, Jean-Marie
PY - 2022/12/5
Y1 - 2022/12/5
N2 - We report the implementation of coordination complexes containing two types of cationic moieties, i. e. pyridinium and ammonium quaternary salt, as potential inhibitors of human cholinesterase enzymes. Utilization of ligands containing NNO-coordination site and binding zinc metal ion allowed mono- and tetra-nuclear complexes to be obtained with corner and grid structural type, respectively, thus affecting the overall charge of the compounds (from +1 to +8). We were able to examine for the first time the multivalency effect of metallosupramolecular species on their inhibitory abilities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Importantly, resolution of the crystal structures of the obtained enzyme-substrate complexes provided a better understanding of the inhibition process at the molecular level. © 2022 Wiley-VCH GmbH.
AB - We report the implementation of coordination complexes containing two types of cationic moieties, i. e. pyridinium and ammonium quaternary salt, as potential inhibitors of human cholinesterase enzymes. Utilization of ligands containing NNO-coordination site and binding zinc metal ion allowed mono- and tetra-nuclear complexes to be obtained with corner and grid structural type, respectively, thus affecting the overall charge of the compounds (from +1 to +8). We were able to examine for the first time the multivalency effect of metallosupramolecular species on their inhibitory abilities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Importantly, resolution of the crystal structures of the obtained enzyme-substrate complexes provided a better understanding of the inhibition process at the molecular level. © 2022 Wiley-VCH GmbH.
KW - acetylcholinesterases
KW - butyrylcholinesterases
KW - inhibitors
KW - supramolecular chemistry
KW - X-ray structures
UR - http://www.scopus.com/inward/record.url?scp=85141202914&partnerID=8YFLogxK
UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85141202914&origin=recordpage
U2 - 10.1002/cbic.202200456
DO - 10.1002/cbic.202200456
M3 - RGC 21 - Publication in refereed journal
C2 - 36193860
SN - 1439-4227
VL - 23
JO - ChemBioChem
JF - ChemBioChem
IS - 23
M1 - e202200456
ER -