Syntheses and PDT activity of new mono- and di-conjugated derivatives of chlorin e₆

Abstract

Syntheses of three new chlorin e 6 conjugates for PDT of tumors are reported. One of the new compounds 17 is conjugated with lysine at the 13 1 -position, but the others are mono-conjugated 14 or diconjugated 15 with the non-amino acid species ethanolamine. Cellular experiments with the three new compounds and previously synthesized non-amino acid 15 2 -conjugates (7–10), 13 1 -monoconjugates 14, 16, and a 13 1 ,15 2 -diconjugate 12 are reported. In vitro cytotoxicity experiments show that the 13 1 -conjugates are more toxic than the 15 2 -conjugates, and the most toxic derivative (dark- and photo-toxicity) is the 13 1 -ethylenediamine conjugate 11. The most useful PDT photosentitizers appear to be the ethanolamine derivatives, conjugated at the 15 2 - and the 13 1 ,15 2 -positions; these show high phototoxicity but relatively low dark toxicity compared with 11, and also the highest dark/photo cytotoxicity ratios.