Síntese, caracterização e avaliação da atividade antimicrobiana de derivados 4h-cromen-5-onas

Abstract

Antimicrobial resistance (AMR) constitutes one of the major current threats to public health, reducing the effectiveness of widely used antimicrobial agents and requiring the development of new therapeutic approaches. In this context, heterocyclic compounds derived from chromenones, have attracted considerable interest in medicinal chemistry due to their structural diversity and the biological potential reported in the literature. The present study aimed to synthesize, structurally characterize, and evaluate the antimicrobial activity of six 4H-chromen5-one derivatives, obtained through multicomponent reactions (MCRs) aligned with the principles of Green Chemistry. The syntheses were carried out using a one-step, catalyst-free methodology involving substituted aromatic aldehydes, cyclic β-dicarbonyl compounds (dimedone or 1,3-cyclohexanedione), and the reagent (E)-N-methyl-1-(methylthio)-2- nitroethenamine (NMSM), resulting in functionalized 4H-chromen-5-one derivatives with satisfactory yields ranging from 75.4% to 84.75% and high synthetic efficiency. The synthesized compounds, designated KA, KB, KC, KD, KE, and KF, were characterized by Nuclear Magnetic Resonance spectroscopy (¹H, ¹³C, and ¹⁹F NMR) and infrared spectroscopy (FTIR-ATR), allowing the unequivocal confirmation of the proposed chemical structures and the assessment of their physicochemical properties. Antimicrobial activity was evaluated by determining the Minimum Inhibitory Concentration (MIC) using the broth microdilution method, in accordance with the guidelines of the Clinical and Laboratory Standards Institute (CLSI), against the bacteria Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. The assays were performed over a concentration range of 0.5 to 256 µg/mL, and MIC values higher than 128 µg/mL were observed for all evaluated derivatives, indicating the absence of significant antimicrobial activity under the tested conditions. Nevertheless, the structural features of the compounds suggest potential for topical applications and for future structural optimization studies. Additionally, the use of multicomponent reactions proved to be an efficient, sustainable, and reproducible synthetic strategy, contributing to the rational generation of molecular libraries and providing a foundation for future investigations into structural optimization and alternative therapeutic applications.