Fluorinated Chromone Derivatives: Synthesis, Theoretical Study, and Evaluation of Their Biological Potential

Abstract

Eight fluorochromones were synthesized and studied in the solid state using vibrational spectroscopy (IR). This investigation was then extended to include the solution phase, using techniques such as ultraviolet–visible (UV–vis) spectroscopy, fluorescence, and cyclic voltammetry. Furthermore, theoretical analyses were conducted using the B3LYP/6–311+G(d,p) method to better understand the molecular properties of these compounds, as well as their UV–vis and IR spectra. All fluorochromones were evaluated in vitro against several human tumor cell lines to determine their anticancer activity, with the nitro and azido derivatives showing generally showing stronger antiproliferative effects than the corresponding amino analogues; chromone 4b exhibited the highest therapeutic index in HeLa cells (TI = 20.3), whereas 6a was the most active derivative overall but displayed low selectivity toward nontumor cells. Molecular docking indicates that the fluorinated chromone derivatives can occupy the STAT3 SH2 binding pocket and interact with key residues involved in ligand recognition. Additionally, the derivatives were tested for their antimicrobial activity against different fungi and strains of clinical bacteria. Selective antifungal activity against Candida species was observed for chromones 4a and 6a, with IC50 values of 20.7–36.2 μM and 8.8–18.3 μM, respectively, while no antibacterial effects were detected under the tested conditions. These results identify 4a and 6a as preliminary, narrow-spectrum antifungal hits against Candida spp.