TY - DATA T1 - New semicarbazones as gorge-spanning ligands of acetylcholinesterase and potential new drugs against Alzheimer’s disease: Synthesis, molecular modeling, NMR, and biological evaluation PY - 2017/12/07 AU - Denise Cristian Ferreira Neto AU - Josélia Alencar Lima AU - Joyce Sobreiro Francisco Diz de Almeida AU - Tanos Celmar Costa França AU - Claudia Jorge do Nascimento AU - José Daniel Figueroa Villar UR - https://tandf.figshare.com/articles/journal_contribution/New_semicarbazones_as_gorge-spanning_ligands_of_acetylcholinesterase_and_potential_new_drugs_against_Alzheimer_s_disease_Synthesis_molecular_modeling_NMR_and_biological_evaluation/5678722 DO - 10.6084/m9.figshare.5678722.v1 L4 - https://ndownloader.figshare.com/files/9929767 KW - Alzheimer’s disease KW - semicarbazones KW - acetylcholinesterase inhibitors KW - NMR Kinetics KW - molecular modeling KW - Ellman’s test N2 - 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. ER -