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

Autor(es)

Almeida, Marlon P. ^[1] ; Kock, Flavio V. C. ^[1] ; de Jesus, Hugo C. R. ^{[1, 2]} ; Carlos, Rose M. ^[1] ; Venancio, Tiago ^[1]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Journal of Inorganic Biochemistry; v. 224, NOV 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/09145-5 - Caracterização de complexos supramoleculares por Ressonância Magnética Nuclear de alta resolução em solução e no estado sólido
• Beneficiário: Tiago Venancio
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/16040-5 - Controle Biorracional de Insetos Pragas
• Beneficiário: Flavio Vinicius Crizostomo Kock
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/21143-0 - Agregados de proteínas amiloides e a relação entre a Doença de Alzheimer e Diabetes tipo 2 investigada por complexos luminescentes de Ru(II)
• Beneficiário: Rose Maria Carlos
• Modalidade de apoio: Auxílio à Pesquisa - Regular