PORPHYRIN DIMERS AS PHOTOSENSITIZERS IN PHOTODYNAMIC THERAPY

被引:95
作者
PANDEY, RK
SMITH, KM
DOUGHERTY, TJ
机构
[1] UNIV CALIF DAVIS,DEPT CHEM,DAVIS,CA 95616
[2] NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,DEPT INNERE MED,DIV RADIAT BIOL,BUFFALO,NY 14263
关键词
D O I
10.1021/jm00169a038
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Porphyrin dimers 9 with ether linkages and possible isomers bis[l-[6,7-bis[2-(methoxycarbonyl)ethyl]-l,3,5,8-tetramethyl-2-vinylporphin-4-yl]ethyl] ether (10) bis[l-[6,7-bis[2-(methoxycarbonyl)ethyl]-l,3,5,8-tetramethyl-4-vinylporphin-2-yl]ethyl] ether (11), and l-[6,7-bis[2-(methoxycarbonyl)ethyl]-l,3,5,8-tetramethyl-2-vinylporphin-4-yl]ethyl l-[6,7-bis[2-(methoxycarbonyl)ethyl]-l,3,5,8-tetramethyl-4-vinylporphin-2-yl]ethyl ether (12) were synthesized from the corresponding (l-hydroxyethyl)vinyldeuteroporphyrin IX dimethyl esters (Hvd). The pure Hvd isomers 2-(l-hydroxyethyl)-4-vinyldeuteroporphyrin IX dimethyl ester (7) and 4-(l-hydroxyethyl)-2-vinyldeuteroporphyrin IX dimethyl ester (8) were obtained from 2-acetyl-4-(l-hydroxyethyl)deuteroporphyrin IX dimethyl ester (3) and 4-acetyl-2-(l-hydroxyethyl)deuteroporphyrin IX dimethyl ester (4). Porphyrins 3 and 4 were prepared either by partial reduction of 2,4-diacetyldeuteroporphyrin IX dimethyl ester (2) or by oxidation of hematoporphyrin IX dimethyl ester (1) by using tetra-n-propylammonium perruthenate (Prn4N)(Ru04) with N-methylmorpholine N-oxide as an oxidizing agent. The in vivo photosensitizing ability and therapeutic ratios of dimers 912 were compared with that of Photofrin II in the SMT-F tumor growing subcutaneously in DBA/2 Ha mice. These dimers were found to have better tumorcidal activity than Photofrin II with reduced skin phototoxicity. © 1990, American Chemical Society. All rights reserved.
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页码:2032 / 2038
页数:7
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