Computational Analysis of Carotenoids Targeting Fibroblast Growth Factor (bFGF) in Comparison with Anti-Angiogenic Drug

Dietary chemical carotenoids are predominantly found in colored foods and consumed worldwide. Carotenoids, whether natural or as supplements, have been shown to possess beneficial health effects, including antioxidant, anti-inflammatory, and anticancer properties; however, their effects on bFGF-mediated angiogenesis and their possible binding to bFGF are unknown. This study investigates the anti-angiogenic activity of some carotenoid substances compared to the authorized anti-angiogenic medicine (regorafenib) using an in silico approach. Key aspects, such as binding affinity, stability, and structural parameters, were evaluated using molecular docking and molecular dynamics simulations (MDS). Additionally, the OSIRIS tool was applied to assess toxicity risk and drug-likeness properties. Docking analysis showed that β-carotene bound strongly to bFGF (-7.5 kcal/mol), comparable to regorafenib (-7.6 kcal/mol), while zeaxanthin displayed moderate affinity (-6.6 kcal/mol), while lutein (-4.4 kcal/mol) and lycopene (-4.1 kcal/mol) exhibited weaker binding. Duplicate MDS confirmed that all carotenoid-bFGF complexes remained structurally stable, exhibiting low root mean square deviation (RMSD)/root mean square fluctuation (RMSF) values, stable radius of gyration (Rg), solvent accessible surface area (SASA), and hydrogen bond numbers similar to or higher than those of regorafenib. OSIRIS property explorer predicted a favorable safety profile for all carotenoids, with zeaxanthin and lutein showing comparatively better drug-likeness. Overall, carotenoids displayed low predicted toxicity and represented promising natural scaffolds for further investigations. These findings are based on computational analysis and require further experimental validation.