Cargando…

Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors

A series of nineteen benzothiazin-4-ones from N-(3-aminopropyl) piperidine, 4-(2-aminoethyl)morpholine or 1-(2-aminoethyl)piperidine, aliphatic or aromatic aldehyde and thiosalicylic acid, were synthesized in good yields by multicomponent one-pot reactions. The solvent was toluene and this efficient...

Descripción completa

Detalles Bibliográficos
Autores principales: Berwaldt, Gabriele A., Gouvêa, Daniela P., da Silva, Daniel S., das Neves, Adriana M., Soares, Mayara S. P., Azambuja, Juliana H., Siqueira, Geonir M., Spanevello, Roselia M., Cunico, Wilson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263113/
https://www.ncbi.nlm.nih.gov/pubmed/30482059
http://dx.doi.org/10.1080/14756366.2018.1543286
_version_ 1783375236701356032
author Berwaldt, Gabriele A.
Gouvêa, Daniela P.
da Silva, Daniel S.
das Neves, Adriana M.
Soares, Mayara S. P.
Azambuja, Juliana H.
Siqueira, Geonir M.
Spanevello, Roselia M.
Cunico, Wilson
author_facet Berwaldt, Gabriele A.
Gouvêa, Daniela P.
da Silva, Daniel S.
das Neves, Adriana M.
Soares, Mayara S. P.
Azambuja, Juliana H.
Siqueira, Geonir M.
Spanevello, Roselia M.
Cunico, Wilson
author_sort Berwaldt, Gabriele A.
collection PubMed
description A series of nineteen benzothiazin-4-ones from N-(3-aminopropyl) piperidine, 4-(2-aminoethyl)morpholine or 1-(2-aminoethyl)piperidine, aliphatic or aromatic aldehyde and thiosalicylic acid, were synthesized in good yields by multicomponent one-pot reactions. The solvent was toluene and this efficient procedure afforded the desired heterocycles in 5 h. Identification and characterization were achieved by NMR and GC–MS techniques. In vitro AChE activities of all compounds were evaluated in cerebral cortex and hippocampus of rats and in general, the results in cortex were more promising than hippocampus. The benzothiazinone 5Bd showed the best AChE inhibition activity IC(50) 8.48 μM (cortex) and IC(50) 39.80 μM (hippocampus). The cytotoxicity of seven compounds in MCR-5 human fibroblast cell by SRB test in 24 h were evaluated and 5Bd suggest preliminary safety, showing no cytotoxicity at 100 µM. Finally, these important findings could be a starting point for the development of new AChE inhibitors agents and will provide the basis for new studies.
format Online
Article
Text
id pubmed-6263113
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-62631132018-12-06 Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors Berwaldt, Gabriele A. Gouvêa, Daniela P. da Silva, Daniel S. das Neves, Adriana M. Soares, Mayara S. P. Azambuja, Juliana H. Siqueira, Geonir M. Spanevello, Roselia M. Cunico, Wilson J Enzyme Inhib Med Chem Short Communication A series of nineteen benzothiazin-4-ones from N-(3-aminopropyl) piperidine, 4-(2-aminoethyl)morpholine or 1-(2-aminoethyl)piperidine, aliphatic or aromatic aldehyde and thiosalicylic acid, were synthesized in good yields by multicomponent one-pot reactions. The solvent was toluene and this efficient procedure afforded the desired heterocycles in 5 h. Identification and characterization were achieved by NMR and GC–MS techniques. In vitro AChE activities of all compounds were evaluated in cerebral cortex and hippocampus of rats and in general, the results in cortex were more promising than hippocampus. The benzothiazinone 5Bd showed the best AChE inhibition activity IC(50) 8.48 μM (cortex) and IC(50) 39.80 μM (hippocampus). The cytotoxicity of seven compounds in MCR-5 human fibroblast cell by SRB test in 24 h were evaluated and 5Bd suggest preliminary safety, showing no cytotoxicity at 100 µM. Finally, these important findings could be a starting point for the development of new AChE inhibitors agents and will provide the basis for new studies. Taylor & Francis 2018-11-27 /pmc/articles/PMC6263113/ /pubmed/30482059 http://dx.doi.org/10.1080/14756366.2018.1543286 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Berwaldt, Gabriele A.
Gouvêa, Daniela P.
da Silva, Daniel S.
das Neves, Adriana M.
Soares, Mayara S. P.
Azambuja, Juliana H.
Siqueira, Geonir M.
Spanevello, Roselia M.
Cunico, Wilson
Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors
title Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors
title_full Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors
title_fullStr Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors
title_full_unstemmed Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors
title_short Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors
title_sort synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263113/
https://www.ncbi.nlm.nih.gov/pubmed/30482059
http://dx.doi.org/10.1080/14756366.2018.1543286
work_keys_str_mv AT berwaldtgabrielea synthesisandbiologicalevaluationofbenzothiazin4onesapossiblenewclassofacetylcholinesteraseinhibitors
AT gouveadanielap synthesisandbiologicalevaluationofbenzothiazin4onesapossiblenewclassofacetylcholinesteraseinhibitors
AT dasilvadaniels synthesisandbiologicalevaluationofbenzothiazin4onesapossiblenewclassofacetylcholinesteraseinhibitors
AT dasnevesadrianam synthesisandbiologicalevaluationofbenzothiazin4onesapossiblenewclassofacetylcholinesteraseinhibitors
AT soaresmayarasp synthesisandbiologicalevaluationofbenzothiazin4onesapossiblenewclassofacetylcholinesteraseinhibitors
AT azambujajulianah synthesisandbiologicalevaluationofbenzothiazin4onesapossiblenewclassofacetylcholinesteraseinhibitors
AT siqueirageonirm synthesisandbiologicalevaluationofbenzothiazin4onesapossiblenewclassofacetylcholinesteraseinhibitors
AT spanevelloroseliam synthesisandbiologicalevaluationofbenzothiazin4onesapossiblenewclassofacetylcholinesteraseinhibitors
AT cunicowilson synthesisandbiologicalevaluationofbenzothiazin4onesapossiblenewclassofacetylcholinesteraseinhibitors