Monocarbonyl curcuminoids as potential photosensitizers in photodynamic therapy against skin cancer

Abstract

Two monocarbonyl dimethylamino curcuminoids, one derived from acetone (C3) and the second one from cyclohexane (C6), were synthesized aiming to study their photophysical properties and anticancer photodynamic potential. Compound C6 exhibited lower absorbance and fluorescence than C3. Photobleaching studies showed that C3 and C6 photostability behavior in DMSO differ significantly. C3 was completely photoconverted into a new species absorbing at lower wavelength than the parent compound, whereas, C6, upon a 30 min irradiation at λ = 440 nm with 15 mW/cm² reached a photostationary phase where a smaller amount of the initial compound coexists with some photoproducts of higher and lower absorbance. Both compounds were able to generate significant amounts of ROS upon irradiation in an aqueous environment and exhibited successful intracellular localization in skin cancer cells (A431 cells). After dark cytotoxicity studies the concentrations of 5 μM and 1 μM for C3 and C6, respectively, were selected for the PDT assessment. C3 presented light dose-dependent photodynamic activity against A431 cells, resulting in 40 % cell viability after 12 min of light irradiation (440 nm, 15 mW/cm²). On the other side, C6 showed a biphasic light dose PDT effect with cell viability gradually decreasing up to 50 % after 5 min of light exposure, and then increasing again after 8 and 12 min of light exposure. The photodynamic performance of C6 may provide a new insight into the development of PSs with reduced prolonged photosensitivity.