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 absorption spectra, proton nuclear magnetic resonance spectra, infrared spectra and mass spectra. The product exhibits stronger red-light absorption and has a much higher photopotentiation factor than HA (i.e., more than 200 versus four at a dose of 4 J cm(-2) of red light on human gastric adenocarcinoma MGC803 cells). The mechanism of phototoxicity of 2-BA-2-DMHA on MGC803 cells irradiated with red light (lambda = 600-700 nm) has also been studied. An examination of extracted cellular DNA by agarose gel electrophoresis shows that the DNA has degraded into fragments with lengths which are multiples of approximately 180-190 base pairs (i.e., oligonucleosome size), a biochemical marker of apoptosis. Transmission electron microscopy reveals chromatin condensation around the periphery of the nucleus, which is also characteristic of apoptosis. 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.