PHOTOSENSITIZING OXONOL DYES WITH ANTINEOPLASTIC ACTIVITY

Three new trimethine oxonol dyes (OX-Y) were synthesized to investigate the influence of the heteroatom (Y = O, S, or Se) in position 2 of the barbituric acid moiety on photophysical characteristics and the potential utility of these dyes as marrow purging agents. Increasing the size of the heteroatom had the expected internal heavy atom effect, facilitating intersystem crossing and thus singlet oxygen production. Surprisingly, fluorescence quantum yields followed a different trend, with OX-S showing the highest and OX-Se the lowest values in both homogeneous solution and liposomes. Calculations of deactivation rates of the first excited singlet state suggested that the rate constant of other non-radiative processes (internal conversion and, possibly, photoisomerization) was about 1 order of magnitude lower for OX-S than for OX-O and OX-Se. Radiative rate constants were identical for all three dyes. Simultaneous exposure to OX-Se or OX-S and light inactivated L1210 and HL-60 leukemia cells in a dose-dependent fashion while OX-O had no effect. OX-Se was markedly more potent than OX-S. When used under conditions that achieved a 5 log reduction of leukemia cells, OX-S/Se-mediated photochemotherapy reduced the capacity of normal bone marrow cells to rescue lethally irradiated mice by less than or equal to 2 log.