Dimeric derivatives of chlorophyll a with fragments of oligoethylene glycols as spacers between macrocycles: Synthesis, dark and photoinduced cytotoxic activity

Abstract

In the present work, new dimeric derivatives of chlorophyll [Formula: see text] with oligoethylene glycol fragments as spacers between macrocycles were synthesized and their dark and photoinduced cytotoxic activities were studied in experiments in vitro. Dimeric derivatives were found to have a relatively low dark cytotoxic activity. It should be noted that most of the studied dimeric derivatives exhibited photoinduced cytotoxic activity at concentrations that were several times lower than those for dark cytotoxic activity. The photoinduced action of one of the most active compounds, a phorbin-chlorin dimer with the triethylene glycol fragment as a spacer between the macrocycles (13), was analysed in more detail in experiments in vitro. Compound (13) was shown to rapidly enter HeLa cells, however, its cytotoxic effect on these cells develops rather slowly. The results of the analysis of the activity of caspase-3 showed that Compound (13) does not cause apoptosis of HeLa cells. Analysis of the degree of hemolysis of mammalian erythrocytes as a result of exposure to Compound (13) showed that plasma membranes are a probable target of this substance.