title: Picket-fence porphyrins as potential phototherapeutic agents.
abstract: The synthetic "picket fence" porphyrin, tetra(o-acetamidophenyl)porphine (TAc), as a biological photosensitizer has been evaluated both in vitro and in vivo in mitochondria from the R3230AC mammary tumor. Studies in vitro, consisting of incubation of mitochondria with TAc at a concentration of 4.0 micrograms/ml followed by photolysis, result in the inhibition of cytochrome c oxidase, proton translocating ATPase, succinate dehydrogenase, and malate dehydrogenase. The diminution in activity of the first three enzymes is approximately 2-fold greater than that seen with Photofrin II under the same conditions. Although TAc exists as four isolable atropisomers, no differences among these different forms were observed in their photosensitized inhibition of mitochondrial enzymes. Administration to tumor-bearing rats of TAc i.p. at a dose of 25 mg/kg did result in accumulation of porphyrin within the mitochondria of the R3230AC tumor as determined by subsequent irradiation of isolated mitochondria. The potential utility of TAc and related porphyrins in cancer phototherapy is discussed.
authors.affiliation: Department of Biochemistry, University of Rochester, School of Medicine and Dentistry, New York 14642.
authors.forename: W J
authors.initials: WJ
authors.lastname: Hagan
authors.forename: D C
authors.initials: DC
authors.lastname: Barber
authors.forename: D G
authors.initials: DG
authors.lastname: Whitten
authors.forename: M
authors.initials: M
authors.lastname: Kelly
authors.forename: F
authors.initials: F
authors.lastname: Albrecht
authors.forename: S L
authors.initials: SL
authors.lastname: Gibson
authors.forename: R
authors.initials: R
authors.lastname: Hilf
mesh_terms: D000818:Animals; D017323:Dihematoporphyrin Ether; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D005260:Female; D006415:Hematoporphyrins / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010778:Photochemotherapy; D011166:Porphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
chemical_list: D006415:Hematoporphyrins; D011166:Porphyrins; D017323:Dihematoporphyrin Ether; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV