Tin(Sn+4)-diiododeuteroporphyrin; an in vitro and in vivo inhibitor of heme oxygenase with substantially reduced photoactive properties.
Iodination of Sn-deuteroporphyrin (Ki = 0.185 microM) at positions C2 and C4 of the porphyrin ring results in an enhanced ability of the resulting derivative, Sn-diiododeuteroporphyrin, to inhibit (Ki = 0.069 microM) heme oxygenase activity in vitro. The potency of Sn-diiododeuteroporphyrin inhibition of bilirubin production in vivo is similar to that of Sn-protoporphyrin, but in vitro tests demonstrate that, when in solution with human serum albumin, Sn-diiododeuteroporphyrin is significantly (3-10 times, depending upon conditions) less photosensitizing than are Sn-protoporphyrin or Sn-mesoporphyrin. These findings demonstrate that halogenation of a suitable porphyrin macrocycle can substantially diminish photoactive properties of the compound whereas retaining its ability to act as a heme oxygenase inhibitor.
Drummond
G S
GS
Rockefeller University Hospital, New York, New York.
Greenbaum
N L
NL
Kappas
A
A
D000622:Aminolevulinic Acid / Q000037:antagonists & inhibitors; D000818:Animals; D000831:Animals, Newborn; D001659:Biliary Tract / Q000187:drug effects / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006932:Hyperbilirubinemia / Q000139:chemically induced / Q000188:drug therapy; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008665:Metalloporphyrins / Q000032:analysis / Q000494:pharmacology*; D010777:Photochemistry; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry / Q000379:methods
D008665:Metalloporphyrins; C055420:tin-2,4-diiododeuterporphyrin; D006418:Heme; D000622:Aminolevulinic Acid; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin