Development of chalcones structure-related to avobenzone: Photoprotection, photostability, and safety evaluation.

Chalcones are α,β-unsaturated ketones with extended π-conjugation, making them promising scaffolds for the development of organic UV filters. In this study, a series of substituted chalcones inspired by the chemical structure of avobenzone (AVO) was synthesized and systematically evaluated for UV absorption profiles, photostability, antioxidant potential, photoprotection, and safety-related properties. Among the compounds, the 2-hydroxychalcones 3ca and 3cb showed the most promising profiles. Chalcone 3ca exhibited λmax at 365 nm, critical wavelength of 386 nm, UVA/UVB ratio of 6.3, and molar absorptivity of 58,880 M-1 cm-1, whereas 3cb showed λmax at 353 nm, critical wavelength of 376 nm, UVA/UVB ratio of 3.2, and molar absorptivity of 28,900 M-1 cm-1. Both compounds fulfilled broad-spectrum protection criteria and showed <5% degradation after UVA and UVB irradiation, with photostability comparable to benzophenone-3 and superior to AVO. Formulations containing 3ca and 3cb reduced UVA-induced DNA damage by 90.4% and 95.1%, respectively. Skin permeation studies demonstrated predominant retention in the stratum corneum (94.1% for 3ca and 97.4% for 3cb), minimal penetration into viable epidermis and dermis, and no detectable compound in receptor fluid. Both chalcones showed no relevant irritation in the HET-CAM assay and no significant alterations in skin biometric parameters after topical application. Collectively, these findings support the potential of hydroxy-substituted chalcones as photostable broad-spectrum UV filters for topical application.