Publication
Chalcones : synthesis, bioactivities and biotransformation
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Abstract(s)
As calconas são compostos carbonílicos a,ß-insaturados que ocorrem na natureza e que apresentam uma ampla variedade de aplicações farmacêuticas e industriais. Devido à cada vez maior atenção que a sociedade tem mostrado pelos problemas ambientais, é altamente recomendável que sejam aplicados métodos de síntese e de transformação mais amigos do ambiente. Um dos métodos ecológicos que pode ser aplicado é a biotransformação, que recorre às capacidades das enzimas e/ou microrganismos para modificar as propriedades biológicas e físico químicas dos compostos. Todos estes factos têm estimulado um grande interesse na síntese, nas atividades biológicas e na biotransformação de calconas.
Neste trabalbo, foram sintetizadas por condensação aldólica, 2'-hidroxicalconas com diferentes padrões de substituição com grupos hidroxilo e metoxilo, usando pela primeira vez hidreto de sódio (NaH) ou LiHMDS como base. O método mais eficiente para a síntese de calconas foi aquele em que NaH foi utilizado como base, mas a desproteção dos grupos hidroxilo diminui acentuadamente o rendimento final. O LiHMDS permitiu a síntese de polibidroxicalconas em apenas um passo, o que é uma vantagem, mas os rendimentos foram baixos.
Os compostos sintetizados foram avaliados pelas suas atividades antioxidante, anticolinesterásica, antibacteriana e antitumoral, e foram estabelecidas relações estruturalatividade, com a 2',4',4 trihidroxicalcona a mostrar ser o composto mais ativo em termos de atividade antioxidante, anti-butirilcolinesterase e antibacteriana. A 4',7-dihidroxiflavanona inibe ambas as colinesterases, o que é bastante interessante em termos de terapia da Doença de Alzheimer.
Também foi efetuada a preparação de um extrato enzimático rico em peroxidase, extraído de Brassica rapa L. bem como a otimização dos seus parâmetros operacionais. Este extrato enzimático não foi capaz de biotransformar nenhuma das calconas testadas, mas catalisa a biotransformação de acetofenonas, que são precursoras do anel aromático A das calconas. Esta biotransformação consiste na bidroxilação do C-6' numa modificação indeterminada no grupo metilo do C-2, as quais só ocorrem se o C-4' já estiver hidroxilado.
ABSTRACT: Chalcones are naturally occurring a,ß-unsaturated carbonyl compounds presenting a wide range of pharmaceutical and industrial applications. Due to our society's increasing attention to environmental problems, the application of eco-friendly methods in synthesis and transformation reactions is higbly desirable. One green approach is biotransformation, which makes use of the capabilities of enzymes and/or microorganisms to modify physicochemical and biological properties of compounds. These facts stimulate vast interest in synthesis, activities and biotransformation of chalcones. ln this work, 2'-hydroxychalcones with different hydroxyl and methoxyl substitution patterns were synthesized by aldol condensation, for the first time using sodium hydride (NaH) or LiHMDS as base. The most efficient method for chalcone synthesis was the one where NaH is the base, but deprotection of hydroxyl groups exerts a marked decrease in the final yield. LiHMDS allowed the one-pot synthesis of polyhydroxychalcones, which is an advantage, but the yields were low. The synthesized compounds were evaluated for antioxidant, anticholinesterasic, antibacterial and antitumor activities, and structure/activity relationships were established, with 2',4',4 trihydroxychalcone being the most active compound in the antioxidant, antibutyrylcholinesterase and antibacterial activities. 4'-7-Dihydroxyflavanone is able to inhibit both cholinesterases, which is very interesting in terms of Alzheimer's Disease therapy. The extraction of a peroxidase rich enzymatic extract from Brassica rapa L. and optimization of its working parameters was also performed. This enzymatic extract is not able to biotransform any chalcone tested but catalyzes the biotransformation of the acetophenones, precursors of chalcones ring A, by hydroxylation of C-6' and an undetermined modification of C-2 methyl group, when the C-4' is hydroxylated.
ABSTRACT: Chalcones are naturally occurring a,ß-unsaturated carbonyl compounds presenting a wide range of pharmaceutical and industrial applications. Due to our society's increasing attention to environmental problems, the application of eco-friendly methods in synthesis and transformation reactions is higbly desirable. One green approach is biotransformation, which makes use of the capabilities of enzymes and/or microorganisms to modify physicochemical and biological properties of compounds. These facts stimulate vast interest in synthesis, activities and biotransformation of chalcones. ln this work, 2'-hydroxychalcones with different hydroxyl and methoxyl substitution patterns were synthesized by aldol condensation, for the first time using sodium hydride (NaH) or LiHMDS as base. The most efficient method for chalcone synthesis was the one where NaH is the base, but deprotection of hydroxyl groups exerts a marked decrease in the final yield. LiHMDS allowed the one-pot synthesis of polyhydroxychalcones, which is an advantage, but the yields were low. The synthesized compounds were evaluated for antioxidant, anticholinesterasic, antibacterial and antitumor activities, and structure/activity relationships were established, with 2',4',4 trihydroxychalcone being the most active compound in the antioxidant, antibutyrylcholinesterase and antibacterial activities. 4'-7-Dihydroxyflavanone is able to inhibit both cholinesterases, which is very interesting in terms of Alzheimer's Disease therapy. The extraction of a peroxidase rich enzymatic extract from Brassica rapa L. and optimization of its working parameters was also performed. This enzymatic extract is not able to biotransform any chalcone tested but catalyzes the biotransformation of the acetophenones, precursors of chalcones ring A, by hydroxylation of C-6' and an undetermined modification of C-2 methyl group, when the C-4' is hydroxylated.
Description
Dissertação de Mestrado, Ciências Biomédicas, 01 de fevereiro de 2018, Universidade dos Açores.
Keywords
Biocatálise Brassica rapa L. (Nabo) Calcona Condensação Aldólica Doença de Alzheimer Química Orgânica Peroxidase Aldol Condensation Bioactivities Biocatalysis Chalcone Peroxidase
Citation
Rosa, Gonçalo Pereira. "Chalcones: synthesis, bioactivities and biotransformation". 2018. 145 p.. (Dissertação de Mestrado em Ciências Biomédicas). Ponta Delgada: Universidade dos Açores, 2017. [Consult. Dia Mês Ano]. Disponível em www:<http://hdl.handle.net/10400.3/4617>.