Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer

Detalhes bibliográficos
Ano de defesa: 2024
Autor(a) principal: Franco, Graziella Dos Reis Rosa lattes
Orientador(a): Viegas Junior, Claudio lattes
Banca de defesa: Franco, Lucas Lopardi, Pacheco, Larissa Helena Lobo Torres, Santos, Jean Leandro Dos, Morcilo, Lucienne Da Silva Lara
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Alfenas
Programa de Pós-Graduação: Programa de Pós-Graduação em Química
Departamento: Pró-Reitoria de Pesquisa e Pós-Graduação
País: Brasil
Palavras-chave em Português:
Área do conhecimento CNPq:
Link de acesso: https://repositorio.unifal-mg.edu.br/handle/123456789/2796
Resumo: Cannabidiol (CBD) is an abundant phytocannabinoid in Cannabis sativa, with no psychotropic effects, that has been intensively studied in recent decades for its biological and medicinal properties. As a result, numerous studies have highlighted its possible therapeutic applications, such as the treatment of cancer, pain, chronic inflammation, neurodegenerative diseases (NDs), epilepsy, depression, and anxiety. Thus, research into NDs, such as Alzheimer's disease (AD) and Parkinson's disease (PD), is gaining a new approach, aimed at symptomatic treatment and finding novel compounds that act by reversing or reducing the characteristic neuroinflammatory condition of these neuropathologies. In this context, this work aimed at the synthesis, characterization, and pharmacological evaluation of new structural analogs of CBD, obtained from R- and S-carvones, seeking to identify their antioxidant, neuroprotective, and cholinesterase inhibitory activities, to identify multifunctional ligands with useful properties for the treatment of NDs, especially AD. As a result, fifty compounds, with novel molecular structures were synthesized. These compounds belong to three different series, namely carvonoyl-cinamoyl-N-acyl-hydrazones CCNA, 26 compounds), oxime-benzamides (OB, 12 compounds), and oxime-cinnamoyl amides (OC, 12 compounds). Among these, 19 compounds were BuChE inhibitors, 13 substances stood out as neuroprotectors, 12 compounds exhibited free radical scavenging activity, and 4 presented a multitarget profile.
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spelling Franco, Graziella Dos Reis Rosahttp://lattes.cnpq.br/1381066386437549Franco, Lucas LopardiPacheco, Larissa Helena Lobo TorresSantos, Jean Leandro DosMorcilo, Lucienne Da Silva LaraViegas Junior, Claudiohttp://lattes.cnpq.br/75339230997893612025-03-27T23:36:09Z2025-04-24T20:14:59Z2025-04-24T20:14:59Z2024-07-05FRANCO, Graziella dos Reis Rosa. Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer. 2024. 303 f. Tese (Doutorado em Química) - Universidade Federal de Alfenas, Alfenas, MG, 2024.https://repositorio.unifal-mg.edu.br/handle/123456789/2796Cannabidiol (CBD) is an abundant phytocannabinoid in Cannabis sativa, with no psychotropic effects, that has been intensively studied in recent decades for its biological and medicinal properties. As a result, numerous studies have highlighted its possible therapeutic applications, such as the treatment of cancer, pain, chronic inflammation, neurodegenerative diseases (NDs), epilepsy, depression, and anxiety. Thus, research into NDs, such as Alzheimer's disease (AD) and Parkinson's disease (PD), is gaining a new approach, aimed at symptomatic treatment and finding novel compounds that act by reversing or reducing the characteristic neuroinflammatory condition of these neuropathologies. In this context, this work aimed at the synthesis, characterization, and pharmacological evaluation of new structural analogs of CBD, obtained from R- and S-carvones, seeking to identify their antioxidant, neuroprotective, and cholinesterase inhibitory activities, to identify multifunctional ligands with useful properties for the treatment of NDs, especially AD. As a result, fifty compounds, with novel molecular structures were synthesized. These compounds belong to three different series, namely carvonoyl-cinamoyl-N-acyl-hydrazones CCNA, 26 compounds), oxime-benzamides (OB, 12 compounds), and oxime-cinnamoyl amides (OC, 12 compounds). Among these, 19 compounds were BuChE inhibitors, 13 substances stood out as neuroprotectors, 12 compounds exhibited free radical scavenging activity, and 4 presented a multitarget profile.O canabidiol (CBD) é um fitocanabinoide abundante em Cannabis sativa, sem efeitos psicotrópicos, e que vem sendo intensamente estudado nas últimas décadas por suas propriedades biológicas e medicinais. Como resultado, inúmeros estudos vêm destacando a possível aplicação terapêutica, a exemplo do tratamento de câncer, dor, inflamações crônicas, doenças neurodegenerativas (DN), epilepsia, depressão e ansiedade. Assim, a pesquisa em DN como doença de Alzheimer (DA) e de Parkinson (DP) ganham uma nova abordagem, visando não somente ao tratamento sintomatológico, mas também mais um caminho na busca por novos compostos que atuem revertendo ou diminuindo o quadro neuroinflamatório característico destas doenças. Neste contexto, o objetivo deste trabalho foi sintetizar, caracterizar e avaliar farmacologicamente novos análogos estruturais do CBD, obtidos a partir das R e S-carvonas, buscando identificar suas atividades antioxidante, neuroprotetora e inibitória de colineterases, buscando identificar ligantes multifuncionais com propriedades úteis ao tratamento de DNs, especialmente a DA. Foram sintetizados 50 compostos com estrutura molecular inédita, a partir de rotas sintéticas com até 3 etapas. Estes compostos estão distribuídos em três diferentes séries, a saber carvonoil-cinamoil-N-acilidrazônicos (CCNA, 26 compostos), oxima-benzamidas (OB, 12 compostos) e oxima-cinamidas (OC, 12 compostos). Dentre esses, 19 compostos foram inibidores da BuChE, 13 substâncias destacaram-se como neuroprotetores e 12 compostos exibiram atividade sequestrante de radicais livres e, 4 substâncias apresentaram um perfil multialvo.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade Federal de AlfenasPrograma de Pós-Graduação em QuímicaUNIFAL-MGBrasilPró-Reitoria de Pesquisa e Pós-Graduaçãoinfo:eu-repo/semantics/openAccessDoenças neurodegenerativasAtividade multifuncionalColinesterasesNeuroinflamaçãoAntioxidantesCIENCIAS EXATAS E DA TERRA::QUIMICASíntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimerinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionreponame:Repositório Institucional da Universidade Federal de Alfenas - RiUnifalinstname:Universidade Federal de Alfenas (UNIFAL)instacron:UNIFALFranco, Graziella Dos Reis RosaLICENSElicense.txttext/plain1987https://repositorio.unifal-mg.edu.br/bitstreams/b1901c7e-9ed3-4065-b165-7d2dfc4692dd/download31555718c4fc75849dd08f27935d4f6bMD51ORIGINALTese de Graziella dos Reis Rosa.pdfapplication/pdf23194139https://repositorio.unifal-mg.edu.br/bitstreams/2cf50da9-b72d-4a72-8d77-68b1a004b931/downloadb262cca75caa277d75d99424a28988aeMD52TEXTTese de Graziella dos Reis Rosa.pdf.txtTese de Graziella dos Reis Rosa.pdf.txtExtracted texttext/plain102078https://repositorio.unifal-mg.edu.br/bitstreams/28ae8d27-9402-4fa8-a5f0-bc999ae65339/download1a92e597f381a9580d83e1f8135aee81MD55THUMBNAILTese de Graziella dos Reis Rosa.pdf.jpgTese de Graziella dos Reis Rosa.pdf.jpgGenerated Thumbnailimage/jpeg2484https://repositorio.unifal-mg.edu.br/bitstreams/82f56662-3b6c-473d-959d-49e1f1fd6d6d/download013da96371fdc2bec308a6b79f159eedMD54123456789/27962026-01-07 14:43:12.219open.accessoai:repositorio.unifal-mg.edu.br:123456789/2796https://repositorio.unifal-mg.edu.brRepositório InstitucionalPUBhttps://bdtd.unifal-mg.edu.br:8443/oai/requestrepositorio@unifal-mg.edu.bropendoar:2026-01-07T17:43:12Repositório Institucional da Universidade Federal de Alfenas - RiUnifal - Universidade Federal de Alfenas (UNIFAL)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
dc.title.por.fl_str_mv Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer
title Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer
spellingShingle Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer
Franco, Graziella Dos Reis Rosa
Doenças neurodegenerativas
Atividade multifuncional
Colinesterases
Neuroinflamação
Antioxidantes
CIENCIAS EXATAS E DA TERRA::QUIMICA
title_short Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer
title_full Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer
title_fullStr Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer
title_full_unstemmed Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer
title_sort Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer
author Franco, Graziella Dos Reis Rosa
author_facet Franco, Graziella Dos Reis Rosa
author_role author
dc.contributor.author.fl_str_mv Franco, Graziella Dos Reis Rosa
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1381066386437549
dc.contributor.referee1.fl_str_mv Franco, Lucas Lopardi
dc.contributor.referee2.fl_str_mv Pacheco, Larissa Helena Lobo Torres
dc.contributor.referee3.fl_str_mv Santos, Jean Leandro Dos
dc.contributor.referee4.fl_str_mv Morcilo, Lucienne Da Silva Lara
dc.contributor.advisor1.fl_str_mv Viegas Junior, Claudio
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/7533923099789361
contributor_str_mv Franco, Lucas Lopardi
Pacheco, Larissa Helena Lobo Torres
Santos, Jean Leandro Dos
Morcilo, Lucienne Da Silva Lara
Viegas Junior, Claudio
dc.subject.por.fl_str_mv Doenças neurodegenerativas
Atividade multifuncional
Colinesterases
Neuroinflamação
Antioxidantes
topic Doenças neurodegenerativas
Atividade multifuncional
Colinesterases
Neuroinflamação
Antioxidantes
CIENCIAS EXATAS E DA TERRA::QUIMICA
dc.subject.cnpq.fl_str_mv CIENCIAS EXATAS E DA TERRA::QUIMICA
description Cannabidiol (CBD) is an abundant phytocannabinoid in Cannabis sativa, with no psychotropic effects, that has been intensively studied in recent decades for its biological and medicinal properties. As a result, numerous studies have highlighted its possible therapeutic applications, such as the treatment of cancer, pain, chronic inflammation, neurodegenerative diseases (NDs), epilepsy, depression, and anxiety. Thus, research into NDs, such as Alzheimer's disease (AD) and Parkinson's disease (PD), is gaining a new approach, aimed at symptomatic treatment and finding novel compounds that act by reversing or reducing the characteristic neuroinflammatory condition of these neuropathologies. In this context, this work aimed at the synthesis, characterization, and pharmacological evaluation of new structural analogs of CBD, obtained from R- and S-carvones, seeking to identify their antioxidant, neuroprotective, and cholinesterase inhibitory activities, to identify multifunctional ligands with useful properties for the treatment of NDs, especially AD. As a result, fifty compounds, with novel molecular structures were synthesized. These compounds belong to three different series, namely carvonoyl-cinamoyl-N-acyl-hydrazones CCNA, 26 compounds), oxime-benzamides (OB, 12 compounds), and oxime-cinnamoyl amides (OC, 12 compounds). Among these, 19 compounds were BuChE inhibitors, 13 substances stood out as neuroprotectors, 12 compounds exhibited free radical scavenging activity, and 4 presented a multitarget profile.
publishDate 2024
dc.date.issued.fl_str_mv 2024-07-05
dc.date.accessioned.fl_str_mv 2025-03-27T23:36:09Z
2025-04-24T20:14:59Z
dc.date.available.fl_str_mv 2025-04-24T20:14:59Z
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dc.identifier.citation.fl_str_mv FRANCO, Graziella dos Reis Rosa. Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer. 2024. 303 f. Tese (Doutorado em Química) - Universidade Federal de Alfenas, Alfenas, MG, 2024.
dc.identifier.uri.fl_str_mv https://repositorio.unifal-mg.edu.br/handle/123456789/2796
identifier_str_mv FRANCO, Graziella dos Reis Rosa. Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer. 2024. 303 f. Tese (Doutorado em Química) - Universidade Federal de Alfenas, Alfenas, MG, 2024.
url https://repositorio.unifal-mg.edu.br/handle/123456789/2796
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dc.publisher.department.fl_str_mv Pró-Reitoria de Pesquisa e Pós-Graduação
publisher.none.fl_str_mv Universidade Federal de Alfenas
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