Computational studies of acetylcholinesterase complexed with fullerene derivatives: a new insight for Alzheimer disease treatment

Abstract

Here, we propose five fullerene (C60) derivatives as new drugs against Alzheimer’s disease (AD). These compounds were designed to act as new human acetylcholinesterase (HssAChE) inhibitors by blocking its fasciculin II (FASII) binding site. Docking and molecular dynamic results show that our proposals bind to the HssAChE tunnel entrance, forming stable complex, and further binding free energy calculations suggest that three of the derivatives proposed here could be potent HssAChE inhibitors. We found a region formed by a set of residues (Tyr72, Asp74, Trp286, Gln291, Tyr341, and Pro344) which can be further exploited in the drug design of new inhibitors of HssAChE based on C60 derivatives. Results presented here report for the first time by a new class of molecules that can become effective drugs against AD.

Keywords:

• fullerene derivatives
• Alzheimer’s disease
• theoretical methodologies
• AChE inhibition
• docking
• molecular modeling

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Brazilian financial agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant number 474757/2012-9]; Fundação de Amparo ao Ensino e Pesquisa do Estado do Rio de Janeiro (FAPERJ) [grant number E-26/102.993/2012]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ Ministério da Defesa (CAPES/MD) Edital PRODEFESA 2008, [grant number PD 1782/2008] for financial support, and the Military Institute of Engineering (IME) and the Federal Institute of Education Science and Technology of Espirito Santo for providing the 80 physical infrastructure and working space. This work was also supported by Excellence project FIM.