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http://hdl.handle.net/1843/69757| Type: | Artigo de Periódico |
| Title: | Two novel donepezil-lipoic acid hybrids: synthesis, anticholinesterase and antioxidant activities and theoretical studies |
| Authors: | Bruna Silva Terra Angelo de Fátima Pedro Henrique Correa da Silva Anna Tramarin Lucas Lopardi Franco Elaine Fontes Ferreira da Cunha Fernando César de Macedo Júnior Teodorico de Castro Ramalho Manuela Bartolini Maria Laura Bolognesi |
| Abstract: | Alzheimer disease (AD) is a complex disease related to multiple pathogenic mechanisms. A strategy to develop effective drugs is based on the so-called multi-target directed ligands (MTDL) by using hybrid compounds. So, in the present study, we have designed and synthesized two hybrids, containing the indanone-piperidine moiety of donepezil, a drug approved for the treatment of AD, and the lipoic acid scaffold, an antioxidant compound endowed with neuroprotective effects. One hybrid was synthesized in four steps with 42% global yield, and the other hybrid in six steps with 19% global yield. The latter hybrid displayed moderate inhibitory activity against human acetylcholinesterase (hAChE) and greater activity against human butyrylcholinesterases (hBuChE). The selectivity for hBuChE was further rationalized by theoretical study. Importantly, the second hybrid showed a good antioxidant activity, exhibiting better ability in scavenging 2,2-diphenyl 1-picrylhydrazyl (DPPH) radicals than lipoic acid. |
| Subject: | Antioxidantes Alzheimer, Doença de Inibidores da colinesterase |
| language: | eng |
| metadata.dc.publisher.country: | Brasil |
| Publisher: | Universidade Federal de Minas Gerais |
| Publisher Initials: | UFMG |
| metadata.dc.publisher.department: | ICX - DEPARTAMENTO DE QUÍMICA |
| Rights: | Acesso Aberto |
| metadata.dc.identifier.doi: | http://dx.doi.org/10.21577/0103-5053.20170196 |
| URI: | http://hdl.handle.net/1843/69757 |
| Issue Date: | 2018 |
| metadata.dc.url.externa: | https://jbcs.sbq.org.br/default.asp?ed=265 |
| metadata.dc.relation.ispartof: | Journal of the Brazilian Chemical Society |
| Appears in Collections: | Artigo de Periódico |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Two Novel Donepezil-Lipoic Acid Hybrids.pdf | 1.55 MB | Adobe PDF | View/Open |
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