Comparative in vivo sensitizing efficacy of porphyrin and chlorin dimers joined with ester, ether, carbon-carbon or amide bonds.
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.
Pandey
R K
RK
Department of Radiation Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Zheng
G
G
Lee
D A
DA
Dougherty
T J
TJ
Smith
K M
KM
D000577:Amides / Q000737:chemistry; D000818:Animals; D002244:Carbon / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D005260:Female; D051379:Mice; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000577:Amides; D004952:Esters; D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin; D002244:Carbon