Synthesis of beta-galactose-conjugated chlorins derived by enyne metathesis as galectin-specific photosensitizers for photodynamic therapy.
A first report on the synthesis and biological evaluation of the beta-galactose-conjugated purpurinimides (a class of chlorins containing a six-membered fused imide ring system) as Gal-1 (galectin-1) recognized photosensitizers, prepared from purpurin-N-propargylimide via enyne metathesis, is discussed. On the basis of examination of the available crystal structure of the galectin-1 N-acetyllactose amine complex, it was considered that the chlorin-based photosensitizers could be introduced into a carbohydrate skeleton to expand the repertoire of the galectin-1-specific ligands. Preliminary molecular modeling analysis utilizing the modeled photosensitizers and the available crystal structures of galectin-carbohydrate complexes indicated that addition of the photosensitizer to the carbohydrate moiety at an appropriate position does not interfere with the galectin-carbohydrate recognition. Under similar drug and light doses, compared to the free purpurinimide analogue, the purpurinimides conjugated either with galactose or with lactose (Gal(beta1-4)-Glc) produced a considerable increase in photosensitizing efficacy in vitro. This indicates the possibility for development of a new class of specific photosensitizers for photodynamic therapy (PDT) based on recognition of a cellular receptor.
Zheng
G
G
Photodynamic Therapy Center, Department of Dermatology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Graham
A
A
Shibata
M
M
Missert
J R
JR
Oseroff
A R
AR
Dougherty
T J
TJ
Pandey
R K
RK
D002241:Carbohydrates / Q000138:chemical synthesis; D005690:Galactose / Q000737:chemistry*; D037161:Galectins; D006388:Hemagglutinins / Q000737:chemistry*; D006801:Humans; D008027:Light; D008958:Models, Molecular; D010778:Photochemotherapy; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002241:Carbohydrates; D037161:Galectins; D006388:Hemagglutinins; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C006969:chlorin; D005690:Galactose