New Chromone Analogues as Potential Bioactive Compounds: Cyclodextrin Complexation and Molecular Docking

Chromone is an important structural motif in numerous biologically active natural and synthetic compounds. The aim of the present study is to synthesize and characterize a series of novel chromone derivatives bearing imidazole and pyrazole moieties. The synthesis involved a two-step procedure in which methyl 3-chromonecarboxylate derivatives were prepared and then condensed with imidazole and pyrazole analogues. The structures of the compounds were characterized using spectroscopy, single-crystal X-ray diffraction and Hirshfeld surface analysis. Compounds 1 and 1A were subjected to ITC titration in DMSO. Anticancer potential of synthetized substances was evaluated against three breast cancer cell lines (MCF-7, MDA-MB-231 and HCC38), and two endometrial cancer cell lines (Ishikawa and Hec-1-A). Compounds 1B and 1C, bearing 3-(1H-imidazol-1-yl)propan-1-amine and3-(3,5-dimethyl-4H-pyrazol-4-yl)propan-1-amine moieties, respectively, exhibited the most pronounced, albeit modest, cytotoxic activity against MCF-7 cells, with IC50 values of approximately 80 μM. In HMEC-1 human microvascular endothelial cells (used as a non-cancerous reference model), the same compounds lowered the signal of the dihydroethidium (DHE) probe, suggesting a modest antioxidant effect; these redox results are reported separately from the anticancer assays. The compounds were subjected to further complex analysis using 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) and molecular docking studies. This complex approach provided a qualitative insight into the structure–activity relationships of the studied derivatives. Given the modest cytotoxicity and limited selectivity of Compounds 1B and 1C, together with their redox-modulating effect observed in HMEC-1 cells, these compounds should be regarded as a starting point for further investigation rather than as promising anticancer candidates.