title: Synthesis, toxicity and biodistribution of two 5,15-di[3,5-(nido-carboranylmethyl)phenyl]porphyrins in EMT-6 tumor bearing mice.
abstract: The total synthesis of a 5,15-di[3,5-(o-carboranylmethyl)phenyl]porphyrin 5, its zinc(II) complex 6, and the corresponding nido-carboranylporphyrins 7 and 8 are reported. The molecular structures of porphyrin 6 and of potassium nido-carborane were obtained and are described. The biodistribution of nido-carboranylporphyrins 7 and 8 in BALB/c mice bearing EMT-6 mammary tumors are presented and compared. Both compounds are effective tumor localizers and delivered therapeutic concentrations of boron to tumors (mean+/-standard deviation): 32.5+/-7.1 and 54.3+/-14 microg/g for 7 and 8, respectively, 2 days after the last of 3 injections of a total boron dose of 23 mg/kg body weight. The zinc(II) complex 8 was found to deliver 1.2-1.7 times higher amounts of boron to tumors than 7, with lower tumor-to-blood boron concentration ratios (9.8/1 and 4.7/1 for 7 and 8, respectively, 2 days after injections). The tumor-to-brain boron concentration ratios were >100/1 for both porphyrins 2 days after administration. Both nido-carboranylporphyrins 7 and 8 were well-tolerated at the concentrations used (75 and 78 mg/kg body weight, respectively) and no morbidity or mortality were observed in these studies.
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA. vicente@lsu.edu
authors.forename: M Graça H
authors.initials: MG
authors.lastname: Vicente
authors.forename: Anura
authors.initials: A
authors.lastname: Wickramasinghe
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Nurco
authors.forename: Hong J H
authors.initials: HJ
authors.lastname: Wang
authors.forename: Marta M
authors.initials: MM
authors.lastname: Nawrocky
authors.forename: Michael S
authors.initials: MS
authors.lastname: Makar
authors.forename: Michiko
authors.initials: M
authors.lastname: Miura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D001895:Boron / Q000032:analysis / Q000737:chemistry; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000378:metabolism*; D008665:Metalloporphyrins / Q000138:chemical synthesis; D051379:Mice; D015394:Molecular Structure; D011166:Porphyrins / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008665:Metalloporphyrins; D011166:Porphyrins; D015032:Zinc; D001895:Boron