Total syntheses of three copper (II) tetracarboranylphenylporphyrins containing 40 or 80 boron atoms and their biological properties in EMT-6 tumor-bearing mice.

Abstract

Three carboranyltetraphenylporphyrins containing 40 or 80 boron atoms were synthesized and evaluated for their biodistribution and toxicity in EMT-6 tumor-bearing mice. Copper (II) meso-5,10,15,20-tetrakis[3-methoxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 6, and copper (II) meso-5,10,15,20-tetrakis[3-hydroxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 8, are B40 congeners with different lipophilicities, each less than their B80 congener, copper (II) meso-5,10,15,20-tetrakis[m-(3,5-di-o-carboranylmethoxybenzyloxy)phenyl]porphyrin, 18. Two days after the last of a series of i.p. injections in BALB/c mice bearing EMT-6 mammary tumors, a dose of 185 mg/kg 6 (54 mg/kg B) delivered over 3.5 times the concentration of boron to tumor (169 microg/g B) than did 118 mg/kg 8 (36 mg/kg B), which delivered 35 microg/g B, or 87 mg/kg 18 (30 mg/kg B), which delivered 46 microg/g B. The tumor-to-blood and tumor-to-brain boron concentration ratios at that time for all three porphyrins exceeded 80:1. Two days after the last injection, there resulted moderate thrombocytopenia that essentially disappeared two days later from 6 and 18, and mild leukocytosis from 6, 8, and 18, all of which were clinically inconsequential. Thus, 6 may rank among the most clinically promising carboranyl porphyrins ever made to deliver 10B to tumors for boron neutron-capture therapy (BNCT) that has also been tested for its toxicity in vivo.

• Authors: Haitao Wu, Peggy L Micca, Michael S Makar, Michiko Miura
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 14 Issue 15 Pg. 5083-92 (Aug 01 2006) ISSN: 0968-0896 [Print] England
• PMID: 16651000 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Boron Compounds
• Metalloporphyrins
• copper (II) meso-5,10,15,20-tetrakis(3-methoxy-4-(o-carboranylmethoxy)phenyl)porphyrin
• Copper

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacokinetics, toxicity)
• Boron Compounds (chemical synthesis)
• Cell Line, Tumor
• Copper (chemistry)
• Disease Models, Animal
• Drug Screening Assays, Antitumor
• Mammary Neoplasms, Experimental (blood supply, drug therapy, metabolism)
• Metalloporphyrins (chemical synthesis, pharmacokinetics, toxicity)
• Mice
• Mice, Inbred BALB C
• Molecular Structure
• Stereoisomerism
• Tissue Distribution
• Transplantation, Heterologous