Comparative in vivo sensitizing efficacy of porphyrin and chlorin dimers joined with ester, ether, carbon-carbon or amide bonds.

Abstract

The anti-cancer activity of dimers joined with ether, ester or carbon-carbon bonds by photodynamic therapy (PDT) was compared by using DBA/2 mice transplanted with SMT/F tumors. Dimers with ether and carbon-carbon linkages were found to be more effective than those linked with ester bonds. Variation of the substituents at peripheral positions made a significant difference in in vivo efficacy. Among the ether and carbon-carbon linked dimers, the divinyl analogs were found to be most effective. The preliminary in vivo results also suggest that the position(s) of the hydrophilic substituents in the molecules make a remarkable difference in photosensitizing activity. An unsymmetrical dimer with an amide linkage, obtained from 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) was found to be less effective than HPPH.