| Hypocrellins, including hypocrellin A (HA) and hypocrellin B (HB), are naturally occurring photosensitizers isolated from the fungus of hypocrella bambuase. Because of their favorable photodynamic properties, hypocrellins present promising application potential in photodynamic therapy (PDT). However, poor water solubility, low absorbance in photodynamic therapeutic window (600-900 nm), and the lacking of affinity towards biomolecules, limit their application in PDT.To enhance the photodynamic properties of HB, the following research has been carried out.(1) A 2-(dimethylamino)ethanethiol-modified HB (DEHB) was designed and synthesized. In neutral buffer solutions tertiary amine end group will be protonated effectively, which on one hand increases the affinity of DEHB to DNA by electrostatic interaction, on the other hand, can improve the water solubility of DEHB. Though DEHB generates singlet oxygen, superoxide anion radical, and semiquinone anion radical less efficiently than EHB (ethanethiol-modified HB), it exhibits higher photodamage ability towards calf thymus DNA than EHB, mainly due to its higher affinity towards CT DNA. Compared with the parent HB, the photodamage capability of DEHB is also enhanced in both aerobic and anaerobic conditions.(2) An adamantane-modified hypocrellin B was designed and synthesized, and was solubilized in aqueous solutions by way of the supramolecular inclusion interaction between the adamantane group andβ-cyclodextrin polymer. ESR experiments showed that the inclusion system of the adamantane-modified hypocrellin B andβ-cyclodextrin polymer remains abilities to generate reactive oxygen species, particularly singlet oxygen.(3) A di-mercaptoacetic acid-modified HB (DMHB) was synthesized by photoreaction. The optimization of reaction conditions, including O2 concentration and the molar ratio between mercaptoacetic acid and HB, increased the yield of the target product from the reported value of 18% to 45%.
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