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

Abstract

Syntheses of three new chlorin e₆ conjugates for PDT of tumors are reported. One of the new compounds <b>17</b> is conjugated with lysine at the 13¹-position, but the others are mono-conjugated <b>14</b> or diconjugated <b>15</b> with the non-amino acid species ethanolamine. Cellular experiments with the three new compounds and previously synthesized non-amino acid 15²-conjugates (<b>7</b>-<b>10</b>), 13¹-monoconjugates <b>14</b>, <b>16</b>, and a 13¹,15²-diconjugate <b>12</b> are reported. <i>In vitro</i> cytotoxicity experiments show that the 13¹-conjugates are more toxic than the 15²-conjugates, and the most toxic derivative (dark- and photo-toxicity) is the 13¹-ethylenediamine conjugate <b>11</b>. The most useful PDT photosentitizers appear to be the ethanolamine derivatives, conjugated at the 15²- and the 13¹,15²-positions; these show high phototoxicity but relatively low dark toxicity compared with <b>11</b>, and also the highest dark/photo cytotoxicity ratios.