Photoactivated cell-killing amino-based flavylium compounds

Abstract

Photodynamic therapy (PDT) is a well-established therapeutic for the treatment of different diseases. The growing interest of this technique required the development of new photosensitizers with better photo-features. This work reports the study of the potential of five nature-inspired amino-based flavylium compounds with different structural features as photosensitizers towards topical PDT. In terms of dark cytotoxicity the five pigments were tested towards confluent skin cells in both fibroblasts and keratinocytes. In the range of concentrations tested (6.3–100 μM), keratinocytes were more prone to growth inhibition and the IC50 values for 5OH4′NMe2, 7NEt2st4′NMe2 and 7NEt24′NH2 were determined to be 47.3 ± 0.3 μM; 91.0 ± 0.8 μM and 29.8 ± 0.8 μM, respectively. 7NEt24′NMe2, 7NEt2st4′NMe2 and 7NEt24′NH2 showed significant fluorescence quantum yields (from 3.40 to 20.20%) and production of singlet oxygen (1O2). These latter chromophores presented IC50 values of growth inhibition of keratinocytes between 0.9 and 1.5 µM, after 10 min of photoactivation with white light. This cellular damage in keratinocyte cells upon white light activation was accompanied with the production of reactive oxygen species (ROS). It was also found that the compounds can induce damage by either type I (ROS production) or type II (singlet oxygen) PDT mechanism, although a higher cell survival was observed in the presence of 1O2 quenchers. Overall, a structure–activity relationship could be established, ranking the most important functional groups for the photoactivation efficiency as follows: C7-diethylamino > C4′-dimethylamino > C2-styryl.

Modulating the thermodynamics, kinetics and photochemistry of 7-diethylamino-4′-dimethylaminoflavylium in water/ethanol, SDS and CTAB micelles

“…Aminoflavylium compounds are an interesting family of compounds exhibiting physicochemical properties suitable for different applications beyond those of anthocyanins in food and health. 1,2,8–10 They could also contribute to a deeper understanding of the anthocyanin multistate of species reported in Scheme 1. Moreover, blue is the most difficult colour to achieve in anthocyanins and bis-aminoflavylium based systems reported in this work exhibit this colour.…”

“…Inspection of this figure shows an equilibrium between the flavylium cation and transchalcone Fig.9b, as well as between trans-chalcone and its anionic form, Fig.9c. The respective acid base constants were calculated by a fitting carried out at three representative wavelengths, Fig.9d, pK AH 2 2+ /AH + = 0.25, pK AH + /Ct = 2.2 and pK Ct/Ct À = 9.0, eqn(8)…”