New cinnamic acid sugar esters as potential UVB filters: Synthesis, cytotoxicity, and physicochemical properties.

Abstract

Cinnamic Acid Sugar Ester Derivatives (CASEDs) are a class of natural compounds that exhibit several interesting biological activities. However, to date, no examples of their use in sunscreen formulations have been reported. Here, we describe the synthesis of a series of novel cinnamic acid esters of glucose (4a-g), ribose (4h) and lactose (4i) starting from the respective acetals 3. The latter were obtained through oxidative alkoxycarbonylation of olefins. For all compounds 3 and 4, UV-Vis spectra were recorded and lipophilicity (i.e., clogP) and cytotoxicity were evaluated. All but one of the synthesized compounds were found to be non-cytotoxic at the concentrations tested and, as expected, absorption spectra depended only on the substituents on the aromatic ring. Finally, the ad hoc synthesized compound 3k, featuring a 4-methoxy substituent on the phenyl ring and a 1,2-O-isopropylidene ribose moiety, provided the most promising results for a possible use as a sunscreen. Indeed, its Sun Protection Factor (SPF), calculated in vitro, was higher with respect to that of ethylhexyl methoxycinnamate (EHMC), which is already utilized in sun care products. Moreover, 3k showed greater antioxidant properties than EHMC, effectively protecting keratinocytes against H₂O₂-induced oxidative damage. At the same time, it showed no cytotoxic effects and preserved cellular metabolic activity and protein content. Based on these results, we believe that CASEDs could find valid applications in the skincare and cosmetics sectors.