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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Probing the acetylcholinesterase inhibitory activity of a novel Ru(II) polypyridyl complex and the supramolecular interaction by (STD)-NMR

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Almeida, Marlon P. [1] ; Kock, Flavio V. C. [1] ; de Jesus, Hugo C. R. [1, 2] ; Carlos, Rose M. [1] ; Venancio, Tiago [1]
Total Authors: 5
[1] Univ Fed Sao Carlos, Chem Dept, Sao Carlos, SP - Brazil
[2] Univ British Columbia UBC, Ctr Blood Res, Life Sci Ctr, 4-420 Life Sci Ctr, 2350 Hlth Sci Mall, Vancouver, BC - Canada
Total Affiliations: 2
Document type: Journal article
Source: Journal of Inorganic Biochemistry; v. 224, NOV 2021.
Web of Science Citations: 0

Currently, acetylcholinesterase (AChE) inhibitors are the only anti-Alzheimer drugs commercially available. Despite their wide use those drugs are all dose dependent and their effect last for no longer than two years, with several side effects. The search of novel acetylcholinesterase (AChE) inhibitors remains as the main scientific route. Here we describe the synthesis, characterization, biological activity and an NMR binding-target study of a novel cis-{[}Ru(Bpy)2(EtPy)2]2+, (RuEtPy), Bpy = 2,2 `-bipyridine and EtPy = 4,2-Ethylamino-pyridine) as a potential AChE inhibitor. The classic Ellman's colorimetric assay suggests that the RuEtPy exhibits a high inhibitory activity, following a competitive mechanism, with a remarkable low inhibition constant (Ki approximate to 16.8 mu M), together with a IC50 = 39 mu M. Hence, we have studied the spatial interactions for this novel candidate towards the human acetylcholinesterase (hAChE) using saturation transfer difference (STD)-NMR, in order to describe the mechanism of the interaction. NMR binding-target results shows that the 4,2-Ethylamino-Pyridine group is spatially closer to hAChE surface chemical arrangement than 2,2 ` bipyridine counterpart, exerting an efficient intermolecular interaction, with a low dissociation constant (KD approximate to 55 mu M), probing that 4,2-Ethylamino-pyridine motif plays a key role in the inhibitory action. (AU)

FAPESP's process: 18/09145-5 - Characterization of supramolecular complexes by solution and solid state high resolution Nuclear Magnetic Resonance
Grantee:Tiago Venancio
Support Opportunities: Regular Research Grants
FAPESP's process: 18/16040-5 - Biorational control of Pest-Insect
Grantee:Flavio Vinicius Crizostomo Kock
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 19/21143-0 - Amyloid protein aggregates and the relationship between Alzheimer's Disease and type 2 Diabetes investigated by Ru(II) luminescent complexes
Grantee:Rose Maria Carlos
Support Opportunities: Regular Research Grants