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Abstract(s)
Os curcuminóides são compostos originados a partir de modificações estruturais feitas na estrutura da curcumina. A curcumina está presente no açafrão-da-índia e tem sido alvo de muitos estudos, pois apresenta diversas atividades biológicas, tais como antioxidantes e antidiabéticas, o que se tem vindo a verificar também nos seus análogos. A presente dissertação teve como objetivo a síntese de análogos da curcumina de forma a melhorar o perfil farmacológico apresentado por esta, mais precisamente a sua biodisponibilidade,
seletividade, estabilidade e capacidade antidiabética.
Numa primeira abordagem foi realizada uma análise in silico de diferentes famílias de análogos da curcumina, bem como estruturas relacionadas, tendo como finalidade perceber a influência das várias modificações estruturais nas propriedades físico-químicas e biológicas dos compostos. Após esta análise foram selecionados os compostos mais promissores para as propriedades em vista evitando, assim, a síntese de compostos com propriedades farmacocinéticas indesejáveis.
Com base na análise in silico realizada, sintetizaram-se com sucesso três grupos de compostos: curcuminóides simétricos, monocurcuminóides e compostos com cadeias β-dicetónicas funcionalizadas na posição α. Para o grupo de compostos monocurcuminóides, foi necessário proceder-se à otimização das condições experimentais. A caracterização dos compostos foi realizada através de técnicas espetroscópicas como RMN (1H, 13C, HSQC), UV-Vis e FT-IR, e ainda através de Difração de Raio-X.
Por fim, a capacidade antioxidante dos compostos foi avaliada de modo a perceber que influência teriam as modificações estruturais feitas nesta propriedade biológica, sendo a curcumina o composto que apresenta maior capacidade antioxidante.
Curcuminoids are compounds originated from structural modifications on the structure of curcumin. Curcumin is present in turmeric and has been the subject of many studies because it presents several biological activities, such as antioxidants and antidiabetics, which has also been verified in its analogues. The present dissertation’s goal is to synthesize curcumin analogues to improve its pharmacological profile, more precisely, its bioavailability, selectivity, stability and antidiabetic capacity. In a first approach, an in silico analysis of different families of curcumin analogues was performed, as well as related structures, in order to perceive the influence of the various structural changes on the physical-chemical and biological properties of the compounds. After this analysis, the most promising compounds for the target properties were selected, thus avoiding the synthesis of compounds with undesirable pharmacokinetic properties. Based on the in silico analysis performed, 3 groups of compounds were successfully synthesized: symmetrical curcuminoids, mono-curcuminoids and compounds with α-functionalized β-dicetonic chains. For the mono-curcuminoid group, the experimental conditions were optimized. The characterization of the compounds was performed by spectroscopic techniques such as NMR (1H, 13C, HSQC), UV-Vis and FT-IR and through X-ray diffraction. Finally, the antioxidant capacity of the compounds was evaluated to understand the influence the structural changes on this biological property, with curcumin being the compound with the highest antioxidant capacity.
Curcuminoids are compounds originated from structural modifications on the structure of curcumin. Curcumin is present in turmeric and has been the subject of many studies because it presents several biological activities, such as antioxidants and antidiabetics, which has also been verified in its analogues. The present dissertation’s goal is to synthesize curcumin analogues to improve its pharmacological profile, more precisely, its bioavailability, selectivity, stability and antidiabetic capacity. In a first approach, an in silico analysis of different families of curcumin analogues was performed, as well as related structures, in order to perceive the influence of the various structural changes on the physical-chemical and biological properties of the compounds. After this analysis, the most promising compounds for the target properties were selected, thus avoiding the synthesis of compounds with undesirable pharmacokinetic properties. Based on the in silico analysis performed, 3 groups of compounds were successfully synthesized: symmetrical curcuminoids, mono-curcuminoids and compounds with α-functionalized β-dicetonic chains. For the mono-curcuminoid group, the experimental conditions were optimized. The characterization of the compounds was performed by spectroscopic techniques such as NMR (1H, 13C, HSQC), UV-Vis and FT-IR and through X-ray diffraction. Finally, the antioxidant capacity of the compounds was evaluated to understand the influence the structural changes on this biological property, with curcumin being the compound with the highest antioxidant capacity.
Description
Trabalho Final de Mestrado para a obtenção do Grau de Mestre em Engenharia Química e Biológica
Keywords
Curcumina Monocurcuminóides Cadeia β-dicetónica Análise in silico Antioxidantes Curcumin Mono-curcuminoids β-diketonic chain in silico analysis Antioxidants
Citation
HENRIQUES, Catarina Alexandra Aires – Curcuminóides com potencial atividade farmacológica: análise in silico, síntese e caracterização. Lisboa: Instituto Superior de Engenharia de Lisboa, 2021. Dissertação de Mestrado.
Publisher
Instituto Superior de Engenharia de Lisboa