Structural related oxidovanadium(IV)-flavonoid complexes. Influence on their anticancer effects

Abstract

Flavonoids, known for their antioxidant properties in plants, can also act as pro-oxidants in cancer cells, an effect that intensifies when coordinated with metal cations. Among them, oxidovanadium(IV) (VO) complexes with flavonoids have shown promising anticancer potential, following a clear relationship of the ligand structure with the activity. Quercetin and troxerutin share a common core structure; however, in troxerutin, four of the five hydroxyl (-OH) groups of quercetin are blocked, which may influence its metal coordination properties. In this study, we synthesized and fully characterized the VOtroxerutin complex using FTIR, EPR, UV–Vis, and reflectance spectroscopies, along with elemental, thermal, and conductivity analyses. Additionally, we prepared the reported VOquercetin complex, which shares the same coordination sphere as VOtroxerutin, to explore a relationship between the structure of the complexes and their activities. Their anticancer potential was tested through in vitro cytotoxicity assays against the A549 human lung cancer cells and HaCaT normal human keratinocytes. Both complexes exhibited anticancer activities (viability inhibition at 100 μM: 32.1 %, VOtroxerutin; 39.5 %,VOquercetin) and selectivity, highlighting their therapeutic potential. Notably, their pro-oxidant effects were activated upon incubation with cancer cells, leading to oxidative stress-induced cytotoxicity and mitochondrial membrane disruption. Further comparisons with the VOrutin complex provided additional insights into the correlation between anticancer activity and the coordination environment of the VOFlavonoid complexes. Additionally, we evaluated the safety profile of VOtroxerutin, finding no acute toxicity or mutagenic effects, supporting its potential as a targeted anticancer therapy with normal cells viability inhibition only at 100 μM (10 %).