New sensitizers for photodynamic therapy: controlled synthesis of purpurins and their effect on normal tissue.
Purpurins are a class of porphyrin derivative that have been shown to have good in vivo cytotoxicity to N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) induced rat bladder tumors (AY-27) implanted into Fisher 344 rats. The synthesis of purpurins from etioporphyrin I and coproporphyrin I proceeds in high yield and with a high degree of regioselectivity. Product formation can be rationalized in terms of relief of steric strain about the periphery of the purpurin macrocycle. The effect of therapeutic light doses using the rat footpad model suggests that, at therapeutic sensitizer doses, normal tissue damage is within acceptable limits, particularly for metalated purpurins.
Morgan
A R
AR
Department of Chemistry, College of Arts and Science, University of Toledo, Ohio 43606.
Rampersaud
A
A
Garbo
G M
GM
Keck
R W
RW
Selman
S H
SH
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003306:Coproporphyrins; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D005044:Etioporphyrins; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D010778:Photochemotherapy; D011166:Porphyrins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis*; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
D003306:Coproporphyrins; D005044:Etioporphyrins; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents