Abstract
Since the FDA approval of tretinoin in 1971, retinoids have been key in treating acne and different skin pathologies. Tazarotene (TZE), a third-generation retinoid and prodrug, is converted in the skin to its active form, tazarotenic acid (TZA). Its structure allows absorption of UVA/UVB light, prompting concerns about potential phototoxicity, but data on the excited state properties of TZE and TZA are still lacking. This work investigates these retinoids' behavior under UVA light exposure through a combined spectroscopic, analytical, and biological approximation. The results show that both compounds form long-lived triplet excited states, which interact with oxygen to produce reactive singlet oxygen. Additionally, TZA interacts with tryptophan (Trp), leading to the formation of a photoproduct with a mass corresponding to a Trp/TZA cyclobutene adduct. These results correlate with reduced cell viability in fibroblasts exposed to light after treatment with TZE or TZA, indicating potential phototoxic effects. Such light-induced reactivity may also be related to the enhanced therapeutic results observed when TZE is used alongside narrow-band UVB phototherapy.