Synthesis and characterization of three novel amphiphilic aminated hypocrellins as photodynamic therapeutic agents.

To improve the amphiphilicities and red absorption of the hypocrellins, three novel 2-amino-2-demethoxy-hypocrellins were synthesized by the mild reactions of hypocrellin B with 4-(2-amino-ethyl)morpholine, N,N-dimethylethylenediamine and 1-(2-amino-ethyl)piperazine, respectively. The structures of these derivatives were characterized with proton nuclear magnetic resonance, infrared and mass spectra (MS). The ultraviolet-visible absorption and fluorescence spectra of the derivatives were measured and the new amino-substituted hypocrellins showed strong absorption in the domain of the phototherapeutic window (600-900 nm). Their amphiphilicities evaluated via the partition coefficients between n-octanol and phosphate-buffered saline buffer improved remarkably. Electron paramagnetic resonance spin-trapping measurements were used to investigate the photodynamic action of the three compounds in the presence of oxygen. Singlet oxygen (1O2) and superoxide anion radical (O2.-) generated by illuminating the hypocrellin derivatives in aerobic solution were observed.