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

• Main Authors: Gabriele A. Berwaldt, Daniela P. Gouvêa, Daniel S. da Silva, Adriana M. das Neves, Mayara S. P. Soares, Juliana H. Azambuja, Geonir M. Siqueira, Roselia M. Spanevello, Wilson Cunico
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-01-01
• Series: Journal of Enzyme Inhibition and Medicinal Chemistry
• Subjects: benzothiazinone; propylpiperidine; acetylcholinesterase; fibroblast cells
• Online Access: http://dx.doi.org/10.1080/14756366.2018.1543286
• ISSN: 1475-6366; 1475-6374

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 IC50 8.48 μM (cortex) and IC50 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.