A NOVEL PHOTOSENSITIZER, 2-BUTYLAMINO-2-DEMETHOXY-HYPOCRELLIN-A (2-BA-2-DMHA) - 1 - SYNTHESIS OF 2-BA-2-DMHA AND ITS PHOTOTOXICITY TO MGC803 CELLS

The reaction of hypocrellin A (HA) with n-butylamine in pyridine under reflux leads to the formation of 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA), which is illustrated by ultraviolet-visible absorpti on spectra, proton nuclear magnetic resonance spectra, infrared spectr a and mass spectra. The product exhibits stronger red-light absorption and has a much higher photopotentiation factor than HA (i.e., more th an 200 versus four at a dose of 4 J cm(-2) of red light on human gastr ic adenocarcinoma MGC803 cells). The mechanism of phototoxicity of 2-B A-2-DMHA on MGC803 cells irradiated with red light (lambda = 600-700 n m) has also been studied. An examination of extracted cellular DNA by agarose gel electrophoresis shows that the DNA has degraded into fragm ents with lengths which are multiples of approximately 180-190 base pa irs (i.e., oligonucleosome size), a biochemical marker of apoptosis. T ransmission electron microscopy reveals chromatin condensation around the periphery of the nucleus, which is also characteristic of apoptosi s. This study suggests that 2-BA-2-DMHA is a potential photosensitizer and that its photoxicity to MGC803 cells proceeds via apoptosis. (C) 1998 Elsevier Science S.A. All rights reserved.