Exploration of a Library of 3,4-(Methylenedioxy)aniline-Derived Semicarbazones as Dual Inhibitors of Monoamine Oxidase and Acetylcholinesterase: Design, Synthesis, and Evaluation.
ChemMedChem
; 11(11): 1145-60, 2016 06 06.
Article
en En
| MEDLINE
| ID: mdl-27135466
ABSTRACT
A library of 3,4-(methylenedioxy)aniline-derived semicarbazones was designed, synthesized, and evaluated as monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors for the treatment of neurodegenerative diseases. Most of the new compounds selectively inhibited MAO-B and AChE, with IC50 values in the micro- or nanomolar ranges. Compound 16, 1-(2,6-dichlorobenzylidene)-4-(benzo[1,3]dioxol-5-yl)semicarbazide presented a balanced multifunctional profile of MAO-A (IC50 =4.52±0.032â
µm), MAO-B (IC50 =0.059±0.002â
µm), and AChE (IC50 =0.0087±0.0002â
µm) inhibition without neurotoxicity. Kinetic studies revealed that compound 16 exhibits competitive and reversible inhibition against MAO-A and MAO-B, and mixed-type inhibition against AChE. Molecular docking studies further revealed insight into the possible interactions within the enzyme-inhibitor complexes. The most active compounds were found to interact with the enzymes through hydrogen bonding and hydrophobic interactions. Additionally, inâ
silico molecular properties and ADME properties of the synthesized compounds were calculated to explore their drug-like characteristics.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Acetilcolinesterasa
/
Semicarbazonas
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Diseño de Fármacos
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Inhibidores de la Colinesterasa
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Monoaminooxidasa
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Inhibidores de la Monoaminooxidasa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
ChemMedChem
Año:
2016
Tipo del documento:
Article
País de afiliación:
India