Chemical natures of 6-formylpterin nucleoside analogs.

Pterin is an electron transfer compound in biological systems. Among the analogs, 6-formylpterin (6FP) has been demonstrated to have many marked physiological activities. In the present study, we have developed the synthetic procedure for nucleoside analogs of 6FP and prepared 1-(beta-D-ribofuranosyl)-2-(N,N-diethylaminomethyleneamino)-6-formylpteridin-4-one (RDEF) and 1-(beta-D-ribofuranosyl)-2-(piperidine-1-ylmethyleneamino)-6-formylpteridin-4-one (RPIF) in which the 1-position is glycosylated. By electron paramagnetic resonance analysis coupled with the DMPO spin trapping technique, it has been elucidated that O2 was converted to H2O2 by RDEF at pH 7.4 in the presence of NADH in the dark. This result indicates that marked reactive oxygen species (ROS) generation activities of 6FP occurring under light illumination, which gives rise to the particular physiological activities such as induction of apoptosis, can be reproduced in the cellular and living systems by such derivatives and gives suggestion for designing pharmaceutical compounds that generate appropriate and controllable amounts of ROS in vivo.