Reação de Povarov aplicada a síntese de 2-(2-piridil)quinolinas antifúngicas
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2017-10-16
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Universidade Federal de Viçosa
Resumo
Compostos com o núcleo piridilquinolina exibem um largo espectro de atividade antifúngica. Neste trabalho, foram sintetizados diversos compostos com esse sistema de anéis conjugados, conhecidos como 2-(2-piridil)quinolinas. Melhorar as suas propriedades farmacêuticas e reduzir a toxicidade para as células humanas normais são os principais desafios. Uma síntese eficiente de 2-(2-piridil)quinolinas foi alcançada por meio da reação de Povarov tricomponente entre anilinas, aldeídos aromáticos e etil vinil éter, na presença de ácido de Lewis [BF 3 .O(CH 3 ) 2 ]. Inicialmente a forma de aquecimento escolhida para o desenvolvimento da síntese de 2-(2- piridil)quinolinas foi o processo convencional e resultou na formação de seis compostos com rendimentos moderados na faixa de 31% a 48%. A fim de aumentar a eficiência da técnica para a síntese de 2-(2-piridil)quinolinas, uma nova fonte de aquecimento foi proposta, utilizando a irradiação por meio de forno de micro-ondas. Após a otimização das condições reacionais foram sintetizados quinze compostos 2- (2-piridil)quinolinas com rendimentos de 30% a 80%. Os compostos sintetizados foram submetidos a ensaios in vitro para avaliação da atividade frente a alguns micro- organismos (fungos e leveduras) clinicamente importantes, incluindo Cryptococcus neoformans e várias espécies do gênero Candida (Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsopolis, Candida krusei). Os resultados dos ensaios antifúngicos foram promissores e em especial vale destacar a 2-(2- piridil)quinolina, que se mostrou um promissor antifúngico para aplicação comercial, apresentando inibição de crescimento acima de 95% contra todas as espécies de Candida testadas e inibição de crescimento acima de 85% contra Cryptococcus neofarms. Este composto apresentou IC 50 de 1,95 g mL -1 contra Candida krusei, resultado superior aos antifúngicos disponíveis comercialmente.
Compounds with the pyridylquinoline nucleus exhibit a broad spectrum of antifungal activity. This dissertation describes the synthesis of novel 2-(2- pyridyl)quinolones. Compounds bearing pharmaceutical properties and reduced toxicity to normal human cells. An efficient synthesis of 2-(2-pyridyl)quinolines was achieved by a three component Povarov reaction between anilines, aromatic aldehydes and ethyl vinyl ether in the presence of Lewis acid [BF 3. O(CH 3 ) 2 ]. Initially the heating form chosen for the development of the synthesis of 2-(2- pyridyl)quinolines was the process by conventional heating and resulted in the formation of six compounds in moderate yields ranging from 31% to 48%. In order to increase the efficiency of the technique for the synthesis of 2-(2- pyridyl)quinolines, a new heating source was proposed using microwave oven irradiation. After the optimization of the reactional conditions, were synthesized fifteen compounds 2-(2-pyridyl)quinolines in yields of 30% to 80% were synthesized. The synthesized compounds were submitted to in vitro assays to evaluate the antifungal activity of some clinically important microorganisms (fungi and yeasts) including Cryptococcus neoformans and various species of the genus Candida (Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsopolis, Candida krusei). The results obtained during the antifungal trials were promising and, in particular, 2-(2-pyridyl)quinoline, which proved to be a promising antifungal with possible commercial application, exhibiting inhibition of growth above 95% against all Candida species tested and inhibition of growth above Of 85% against Cryptococcus neofarms. This compound showed an IC 50 of 1,95 μg mL -1 against Candida krusei, a result superior to commercially available antifungal agents.
Compounds with the pyridylquinoline nucleus exhibit a broad spectrum of antifungal activity. This dissertation describes the synthesis of novel 2-(2- pyridyl)quinolones. Compounds bearing pharmaceutical properties and reduced toxicity to normal human cells. An efficient synthesis of 2-(2-pyridyl)quinolines was achieved by a three component Povarov reaction between anilines, aromatic aldehydes and ethyl vinyl ether in the presence of Lewis acid [BF 3. O(CH 3 ) 2 ]. Initially the heating form chosen for the development of the synthesis of 2-(2- pyridyl)quinolines was the process by conventional heating and resulted in the formation of six compounds in moderate yields ranging from 31% to 48%. In order to increase the efficiency of the technique for the synthesis of 2-(2- pyridyl)quinolines, a new heating source was proposed using microwave oven irradiation. After the optimization of the reactional conditions, were synthesized fifteen compounds 2-(2-pyridyl)quinolines in yields of 30% to 80% were synthesized. The synthesized compounds were submitted to in vitro assays to evaluate the antifungal activity of some clinically important microorganisms (fungi and yeasts) including Cryptococcus neoformans and various species of the genus Candida (Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsopolis, Candida krusei). The results obtained during the antifungal trials were promising and, in particular, 2-(2-pyridyl)quinoline, which proved to be a promising antifungal with possible commercial application, exhibiting inhibition of growth above 95% against all Candida species tested and inhibition of growth above Of 85% against Cryptococcus neofarms. This compound showed an IC 50 of 1,95 μg mL -1 against Candida krusei, a result superior to commercially available antifungal agents.
Descrição
Palavras-chave
Síntese orgânica, Compostos orgânicos, Quinolinas -Sínteses
Citação
BOREL, Carmindo Ribeiro. Reação de Povarov aplicada a síntese de 2-(2-piridil)quinolinas antifúngicas. 2017. 186 f. Tese (Doutorado em Agroquímica) - Universidade Federal de Viçosa, Viçosa. 2017.