Highly diversified fluorinated chromane-thiadiazol-saturated cyclic amine hybrids: Design, synthesis, single crystal XRD and MCF-7 Cell-line Study

The current study focuses on the synthesis and characterization of novel fluorinated chromane derivatives, aiming to explore their structural and biological potential. The molecular framework integrates fluorine for enhanced physicochemical properties, employing nucleophilic substitution and cyclization strategies. The synthesized derivatives (4a–4j) were characterized using advanced spectroscopic methods (¹H NMR, ¹⁹F NMR, ¹³C NMR, and mass spectrometry) and crystallographic analysis, confirming their structural core. Biological evaluations against MCF-7 breast cancer cells revealed significant cytotoxicity, with compounds 4 g and 4f demonstrating superior activity (IC₅₀: 2.73 µM and 3.81 µM, respectively) compared to the standard sunitinib (IC₅₀: 5.00 µM). SAR analysis highlights the role of specific cycloaliphatic and polar substituents in enhancing activity. Additionally, docking studies targeting VEGFR2 elucidated key binding interactions, corroborating the compounds' potential as anticancer agents. This work showed the incorporation of fluorine and the rational design of fluorinated scaffolds for drug development.