New Hybrid Benzothiazole Derivatives from Gallic and Syringic Acid as a Potential Multifunctional Skin Disease.

Multifunctional drugs represent an emerging strategy for treating complex skin disorders and melanoma. A series of benzothiazole-based hybrids incorporating gallic and syringic acid moieties was synthesized and evaluated as multifunctional agents for skin-related applications. Six hydrazone (GAHYDR1-3) and acyl-hydrazone (GACIN1-3) derivatives were obtained and fully characterized. Hydroxylated compounds showed the strongest antioxidant activity, with GAHYDR1 and GACIN1 displaying low DPPH IC50 values and high FRAP reducing power. UV-Vis studies revealed strong UVA-UVB absorption, with molar extinction coefficients comparable to or exceeding those of PBSA. Photoprotective evaluation showed SPF values up to 10.09 (GACIN2) and broad-spectrum behavior for selected derivatives. Antioxidant activity remained substantially stable over 3 months in solution. Antiproliferative assays against Colo38, A375, and HaCaT cell lines indicated generally low cytotoxicity toward non-tumor cells. Notably, GAHYDR3 exhibited selective activity against A375 melanoma cells (IC50 = 8.75 µM; SI = 8.12). Overall, phenolic substitution emerged as a key determinant of biological activity, highlighting hydroxylated benzothiazole hybrids as promising antioxidant and photoprotective agents, with GAHYDR3 representing a potential lead for anti-melanoma development.