Fluoróforos bioativos baseados em n-heterociclos funcionalizados com ácido carboxílico: síntese, caracterização, estudo óptico e avaliação da atividade biológica

Abstract

This study describes the synthesis, structural and optical characterization, and antimicrobial and anticancer activity of compounds of four classes: a) quinoxalines: derivatives of 2,3-diaryl-4-carboxylic acid, the 6 molecules obtained, one of which was new, presented fluorescence in the solid state and/or solutions with AIE properties studied in organic solvent/water mixtures, promoted by the restriction of intramolecular motions (RIM) mechanism and varying due to the presence of long alkyl chains and alkoxy donor groups. The compounds also presented positive solvatochromism in the fluorescence emission spectra and the potassium salt of QX1 was an excellent AIEogen in water/THF mixture. The importance of the carboxylic acid group was studied from infrared (IR) spectra and theoretical calculations were performed considering the implicit effects of the solvent. b) quinolines: 5 of which were new, 8 of the 10 styrylquinoline-4-carboxylic acid derivatives showed interesting optical properties varying according to the substitution pattern of these compounds. The solvatochromic behavior was studied in 10 solvents with different polarities and the quantitative study of the solute-solvent interactions was performed. O-acetylated compounds showed acidochromism both with addition of acid in the methanol solution and in buffered solutions with different pH values, making them strong candidates for fluorescent probes in physiological media. c) dihydroquinolines: 2 new derivatives of 1,2-dihydroquinoline-4-carboxylic acid were obtained by a new method. The compounds were fluorescent in solid phase and the AIE study was also performed, in addition to the analysis in buffered solutions with different pH values. d) pyrazines: 4 1,2-dicyanopyrazines derivatives were rapidly obtained in a microwave reactor and their optical properties were quite similar to those of quinoxalines with the same substitution pattern, but with lower quantum yield values. Of all the compounds evaluated for antimicrobial activity, most quinoxalines and quinolines showed excellent results, with MIC values even lower than those of the reference drugs, with their mechanism of action studied through inverse virtual screening (IVS) and molecular docking.