Butylamino-demethoxy-hypocrellins and photodynamic therapy decreases human cancer in vitro and in vivo

2-Butylamino-2-demethoxy-hypocrellin A (BAHA) and B (BARB) are new photosensitizers synthesized by a mild reaction of hypocrellins and butylamine. In BAHA and BAHB, the peri-hydroxylated perylenequinone structure of the parent hypocrellins is preserved and the red absorption is enhanced distinctly. Electron paramagnetic resonance spin trapping measurements and 9,10-diphenylanthracene bleaching studies were used to investigate the photodynamic action of BAHA and BARB in the presence of oxygen. Singlet oxygen (O-1(2)) and superoxide anion radical (O-2(.-)) produced by illuminating BAHA and BARB in aerobic solution have been observed. Compared with hypocrellin A and B, BAHA and BAHB primarily remained able to generate O-1(2) and enhanced distinctly the O-2(.)-generating abilities. The photodynamic action of BAHA and BAHB in the therapy of cancer was investigated in vitro and in vivo. Both in vitro and in vivo results revealed a significant decrease in cancer cell growth. Laser or dye alone had no effect, indicating that intratumor BAHA and laser therapy may prove useful in unresectable cancer. (C) 2001 Elsevier Science B.V. All rights reserved.