Butylamino-demethoxy-hypocrellins and photodynamic therapy decreases human cancer in vitro and in vivo.
2-Butylamino-2-demethoxy-hypocrellin A (BAHA) and B (BAHB) 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 BAHB in the presence of oxygen. Singlet oxygen (1O2) and superoxide anion radical (O2(*-)) produced by illuminating BAHA and BAHB in aerobic solution have been observed. Compared with hypocrellin A and B, BAHA and BAHB primarily remained able to generate 1O2 and enhanced distinctly the O2(*-)-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.
Xu
S
S
Center for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, PR China.
Chen
S
S
Zhang
M
M
Shen
T
T
Zhao
Y
Y
Liu
Z
Z
Wu
Y
Y
D000818:Animals; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010569:Perylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use* / Q000633:toxicity; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011809:Quinones / Q000138:chemical synthesis / Q000627:therapeutic use* / Q000633:toxicity
C114700:2-butylamino-2-demethoxy-hypocrellin A; C437043:2-butylamino-2-demethoxy-hypocrellin B; D017319:Photosensitizing Agents; D011809:Quinones; D010569:Perylene