Polyamine conjugates of meso-tritolylporphyrin and protoporphyrin IX: potential agents for photodynamic therapy of cancers.
An efficient five-step synthesis method was developed to obtain tritolylporphyrin and protoporphyrin IX polyamine conjugates. These compounds were composed of either one polyamine unit (spermidine or spermine) covalently tethered to monocarboxyphenyl tritolylporphyrin or two molecules of polyamines borne by protoporphyrin IX. In each compound, an aliphatic spacer arm is linked to the N(4) polyamine position. Photocytotoxicity of these new compounds was evaluated against K562 human chronic myelogenous leukemia cells and compared to Photofrin II; protoporphyrin IX polyamine conjugates exhibited much stronger photocytocicity than Photofrin II and were shown to readily induce necrosis in treated cells.
Sol
Vincent
V
Université de Limoges, Faculté des Sciences et Techniques, Laboratoire de Chimie des Substances Naturelles (LCSN), France.
Lamarche
François
F
Enache
Michaela
M
Garcia
Guillaume
G
Granet
Robert
R
Guilloton
Michel
M
Blais
J C
JC
Krausz
Pierre
P
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000628:therapy; D009336:Necrosis / Q000139:chemically induced; D010778:Photochemotherapy; D011073:Polyamines / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology; D011524:Protoporphyrins / Q000737:chemistry* / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared; D013095:Spermidine / Q000737:chemistry / Q000494:pharmacology; D013096:Spermine / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011073:Polyamines; D011166:Porphyrins; D011524:Protoporphyrins; D013096:Spermine; D017323:Dihematoporphyrin Ether; C028025:protoporphyrin IX; D013095:Spermidine