Synthesis Of Aminated Hypocrellins And Study On Their Photodynamic Activities

Hypocrellins, isolated from the parasitic fungus Hypocrella bambuase sacc, are efficient phototherapeutic agents and photosensitizers. Studies indicate that they have significant anti-tumor and antiviral activities. In this paper they have been investigated in the following respects.1. One of the deficiency that limits hypocrellins' use in photodynamic therapy is that they do not display sufficiently strong absorption in phototherapeutic window (600 ~ 900nm), in which tissue penetration is maximal. We synthesized three novel amrnoniated hypocrellin B derivatives by the mild reactions. Their structures were characterized with proton nuclear magnetic resonance spectra, infrared spectra and mass spectra. The substitution occurs at position 2 or 11 of hypocrellin B. The UV-vis absorption spectra of the derivatives were measured and the new ammo-substituted hypocrellins showed strong absorption in the domain of the phototherapeutic window (600~900nm).2. Their amphiphilicities evaluated via the partition coefficients (PC) between n-octanol and PBS buffer improved remarkably. The results indicate that they preserve the hypocrellins' lipid-solubility with enhanced water-solubility, which may solve the problem of difficult pharmaceutical preparation in photodynamic therapy.3. The fluorescence spectra of these aminated derivatives excited at 460 nm were measured and a new fluorescent band at longer wavelength (around 700 nm) appeared, along with decreased fluorescence intensity of the dyes due to the introduction of the amino groups. The new fluorescent band is considered to be related to the intramolecular charge transfer between the amino group and the quinonoid carbonyl group.4. The active oxygen species generated by the three novel aminated hypocrellinswere detected by electron paramagnetic resonance (EPR) spin trapping measurements. Their generation abilities of singlet oxygen and superoxide anion radical are both lower than hypocrellin B. The possible reason may be that the addition of amino group induces fast intramolecular electron transfer and destroys intramolecular H-atom transfer process in peri-hydroxy perylenequinon ring.5. The absorption and fluorescence spectra of butylaminated and ethylenediaminated hypocrellins were investigated and compared with hypocrellin. It is confirmed that the longer wavelength bands of hypocrellin and the fluorescent state of hypocrellin are all derived from the intramolecular H-atom transfer process between the peri-hydroxyl group and the quinonoid carbonyl group. Introduction of amino groups enlarges the absorption spectra and fluorescence spectra of HB. The distinct solvents-dependence of their absorption and emission spectra indicates that the longer wavelength bands of aminated hypocrellins derive from intramolecular charge transfer process.