Photosensitizers related to purpurin-18-N-alkylimides: a comparative in vivo tumoricidal ability of ester versus amide functionalities

For a comparative study, 3-(alkyloxyethyl)-3-devinylpurpurin-18-N-hexylimides with ester and amide functionalities were investigated for tumor selectivity and in vivo photosensitizing efficacy. Compared to amide analogues, the related photosensitizers with ester functionalities were found to be more effective. Among these compounds the 3-devinyl-(3-hexyloxyethyl)-purpurin-18-N-hexylimide as methyl ester 12 showed excellent tumor uptake (tumor versus muscle ratio: 8:1), and produced 100% tumor cure on day 30 at a dose of 1.0 μmol/kg. The mice were treated with light (135 J/cm2, 705 nm) at 24 h post injection of the drug. Scheme 1. (a) Zn(Br)2/HMDS, hexylamine, toluene, reflux; (b) HBr/AcOH; (c) alkyl alcohol; (d) alkyl amine; (e) CH2N2; (g) MeOH/KOH; (f) aq LiOH/MeOH/THF; (g) DCC/H2N–(CH2)5CH3.