Multifunctional Bioactivity of Halolactones Derived from Vanillin and Their Effects on Lipid Membranes: Biological and Biophysical Evaluation

A series of novel vanillin-derived halolactones bearing a phenolic ring at the β-position were comprehensively evaluated for their antioxidant and anti-inflammatory properties. The most active derivative, trans-4-(4′-hydroxy-3′-methoxyphenyl)-5-(1-iodoethyl)dihydrofuran-2(3H)-one (LV2), exhibited strong antioxidant activity in the ABTS assay (EC50 = 35.65 ± 2.34 μM), comparable with Trolox® and superior to the reference compound in the UV-C-induced oxidative stress assay (IC50 = 48.67 ± 5.46 μM). Among the tested lactones, LV2 showed moderate anti-inflammatory activity in the COX-1 and COX-2 inhibition assays. Further studies revealed that iodolactone LV2 exhibited high antiproliferative activity in the MTT assay, particularly against the LM-MEL-75 and EPG85-257RDB cell lines (IC50 = 8.67 ± 10.61 μM and 7.37 ± 3.23 μM, respectively), along with high selectivity (selectivity indices > 5). The effects of iodolactone LV2 on various lipid membranes were examined using fluorometric methods, while its impact on human red blood cell morphology was evaluated by analyzing erythrocyte shape changes. The influence of LV2 on model membrane organization was further investigated using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). All spectroscopic studies confirmed the lactone’s interaction with polar regions of model membranes, demonstrating its capacity to modulate membrane-associated functions. This multifunctional bioactivity positions iodolactone LV2 as a promising candidate for further anticancer studies.