Two new compounds (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dihydroacridin-1(2H)-ylidene)hydrazinecarbothiomide (3) and (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dhihydroacridin-1(2H)-ylidene)hydrazinecarboxamide (4) were synthesized and evaluated for their anticholinesterase activities. In vitro tests performed by NMR and Ellman's tests, pointed to a mixed kinetic mechanism for the inhibition of acetylcholinesterase (AChE). This result was corroborated through further docking and molecular dynamics studies, suggesting that the new compounds can work as gorge-spanning ligands by interacting with two different binding sites inside AChE. Also, in silico toxicity evaluation suggested that these new compounds can be less toxic than tacrine.

c Laboratory of Molecular Modeling Applied to Chemical and Biological Defense Military Institute of Engineering Praia Vermelha Rio de Janeiro 22290 270 Brazil

c Laboratory of Molecular Modeling Applied to Chemical and Biological Defense Military Institute of Engineering Praia Vermelha Rio de Janeiro 22290 270 Brazil d Center for Basic and Applied Research Faculty of Informatics and Management University of Hradec Kralove Hradec Kralove Czech Republic

e Institute of Biosciences Federal University of the State of Rio de Janeiro Urca Rio de Janeiro 22290 240 Brazil

Medicinal Chemistry Group Military Institute of Engineering Praia Vermelha Rio de Janeiro 22290 270 Brazil

Medicinal Chemistry Group Military Institute of Engineering Praia Vermelha Rio de Janeiro 22290 270 Brazil b Department of Chemistry Federal University of Roraima Boa Vista Roraima 69310 000 Brazil

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