Síntese e avaliação da atividade larvicida de ácidos quinolino-4-carboxílicos derivados da 5-flúor-isatina e acetofenonas substituídas

Abstract

Dengue, Zika and Chikungunya are arboviruses, transmitted by the Aedes aegypti mosquito, which cause symptoms such as fever, headache and, in some cases, even death, being a health problem not only in Brazil, but also throughout the world. The fight against these diseases is based on mosquito population control, since vaccines are not yet fully effective. One class of compounds that possess a wide range of biological activity are quinoline-4-carboxylic acids (AQ4C’s). These compounds can be obtained through the Pfitzinger reaction, a reaction involving isatin and a carbonyl compound a-methylene. Thus, this work aimed to synthesize, characterize through physical methods such as 1H and 13C NMR and evaluate the larvicidal activity of 11 quinoline-4-carboxylic acids, 4 of which are unpublished, derivatives of 5-fluoro-isatin and substituted acetophenones. with electron donating and withdrawing groups, in addition to carrying out an in silico study, evaluating physicochemical parameters relevant to the oral bioavailability of these compounds. The AQ4C's were obtained through the proposed methodology, using a basic solution of potassium hydroxide (KOH 30% w/v) in a reflux system, at a temperature of 100°C in an oil bath, over a period of time that varied from 4 to 24 hours, with yields that were in the range of 70%-98%. All synthesized compounds had structural confirmation by physical characterization methods and in silico data showed that they all comply with Lipinski's rule. The solvatochromism study was carried out for 6-fluoro-2-(4-methoxyphenyl)quinoline-4-carboxylic acid where there was a tendency for bathochromic shift with the increase in the dielectric constant of the polar aprotic solvents used and a hypsochromic shift in the polar protic solvent. . The compound showed good quantum yield values when compared to the standard used (quinine sulfate), with ΦF ranging from 19.9% to 35.4%. An investigation was carried out on the larvicidal activities of AQ4C's against the larvae of the Aedes aegypti mosquito. Some compounds showed strong larvicidal activity after 72 hours when using a concentration of 100ppm, resulting in a lethality rate of 99% and 100%. The LC50 value of 3 compounds was obtained, which presented values of 181.97, 61.66 and 34.67 ppm, with 6-fluoro-2-(4-hydroxyphenyl)quinoline-4-carboxylic acid being the most active of the series investigated.