Síntese e atividade antiproliferativa de isocurcuminoides monocetônicos.
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Data
2021-12-02
Autores
Kandjamba, Dinis Caina
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O câncer é um conjunto de enfermidades caracterizadas pelo crescimento rápido e desordenado das células tumorais, sendo causador de numerosos danos para a saúde ao redor do mundo. Esforços múltiplos têm sido realizados no combate do câncer e também a busca por novas terapias mais eficazes tem sido constante. Contudo, apesar de vários tratamentos quimioterápicos para combater a neoplasia estar em desenvolvimento nos últimos anos, são enormes as buscas por novos agentes antineoplásicos que atuam contra as células tumorais, de formas a atenuarem os efeitos adversos do tratamento. A curcumina é um pigmento amarelo que está presente no açafrão, possui elevado espectro de atividades biológicas, entre as quais destaca-se a sua ação antineoplásica. Mas alguns fatores, químicos e farmacológicos, a exemplo da instabilidade química/fotoquímica e a baixa biodisponibilidade comprometem seu uso terapêutico. De formas a contornar esses desafios, estratégias têm sido feitas com objetivos de otimizar esses parâmetros, usando a permutação do fragmento β-dicetona, agente causador dessas limitações, pelo grupo monocarbonila, gerando assim, os análogos simplificados monocetônicos. Neste trabalho, foram planejados e sintetizados 20 análogos isocurcuminóidicos monocetônicos, com rendimento que variou entre 34% a 93%. Os análogos sintetizados foram caracterizados e confirmados por análise de Ressonância Magnética Nuclear de Hidrogênio e Carbono-13. Dos análogos sintetizados, treze foram submetidos a análise de pureza, a qual variou entre 97% a 99%. O log P foi medido por HPLC com valores a variarem na faixa de 1,66 a 3,54. Os ensaios biológicos dos compostos sintetizados foram feitos contra células humanas HCT116. Por tanto, o uso de Isocurcumóidicos monocetônicos permitiu inferir sobre a importância de curcuminoides para a atividade antiproliferativa.
Cancer is a set of diseases characterized by fast and disordered growth of cells, causing numerous damages to health around the world. Multiple efforts have been used to combat the cancer and the search for new and more effective therapies have been constant. Therefore, despite the fact that several chemotherapy treatments to combat cancer have been under development in recent years, there are huge searches for new antineoplastic agents that act against tumor cells, in order to attenuate the adverse effects of the treatment. Curcumin is a yellow pigment that is present in turmeric, it has a high spectrum of biological activities, among which its antineoplastic action stands out. However, some chemical and pharmacological factors, such as chemical/photochemical instability and low bioavailability compromise its therapeutic use. In order to overcome these challenges, strategies have been developed with the objective of optimizing these parameters, using the replacement of β-diketone unit, the agent causing these limitations, by the monocarbonyl group, thus generating the simplified monoketone analogues. In this work, 20 monoketone Isocurcuminoids analogues were designed and synthesized, with reaction yields ranging from 34% to 93%. The synthesized analogues were characterized and confirmed by Hydrogen and Carbon-13 Nuclear Magnetic Resonance. Of the synthesized analogues, thirteen were subjected to purity analysis, which ranged from 97% to 99%. Log-P was measured by HPLC with values ranging in the range from 1.66 to 3.54. Biological assays of the synthesized compounds were performed against human HCT116 cells. Therefore, the use of monoketone isocurcumoids allowed us to infer about the importance of curcuminoids for antiproliferative activity.
Cancer is a set of diseases characterized by fast and disordered growth of cells, causing numerous damages to health around the world. Multiple efforts have been used to combat the cancer and the search for new and more effective therapies have been constant. Therefore, despite the fact that several chemotherapy treatments to combat cancer have been under development in recent years, there are huge searches for new antineoplastic agents that act against tumor cells, in order to attenuate the adverse effects of the treatment. Curcumin is a yellow pigment that is present in turmeric, it has a high spectrum of biological activities, among which its antineoplastic action stands out. However, some chemical and pharmacological factors, such as chemical/photochemical instability and low bioavailability compromise its therapeutic use. In order to overcome these challenges, strategies have been developed with the objective of optimizing these parameters, using the replacement of β-diketone unit, the agent causing these limitations, by the monocarbonyl group, thus generating the simplified monoketone analogues. In this work, 20 monoketone Isocurcuminoids analogues were designed and synthesized, with reaction yields ranging from 34% to 93%. The synthesized analogues were characterized and confirmed by Hydrogen and Carbon-13 Nuclear Magnetic Resonance. Of the synthesized analogues, thirteen were subjected to purity analysis, which ranged from 97% to 99%. Log-P was measured by HPLC with values ranging in the range from 1.66 to 3.54. Biological assays of the synthesized compounds were performed against human HCT116 cells. Therefore, the use of monoketone isocurcumoids allowed us to infer about the importance of curcuminoids for antiproliferative activity.
Descrição
Palavras-chave
Curcumina, Curcuminoides, Análogos monocetônicos, Curcumin, Curcuminoid, Monoketonic analogues