Synthesis and Comparative Toxicology of a Series of Polyhedral Borane Anion-Substituted Tetraphenyl Porphyrins

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• 作者：Myoung-Seo Koo ; Tomoko Ozawa ; Raquel A. Santos ; Kathleen R. Lamborn ; Andrew W. Bollen ; Dennis F. Deen ; Stephen B. Kahl
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：February 22, 2007
• 年：2007
• 卷：50
• 期：4
• 页码：820 - 827
• 全文大小：96K
• 年卷期：v.50,no.4(February 22, 2007)
• ISSN：1520-4804

文摘

Three structurally similar tetraphenylporphyrins bearing polyhedral borane anions have been synthesizedand their toxicological profiles obtained in rats. These conjugates were found to have quite different acutetoxicities as manifested at the maximum tolerated dose (MTD). When given at the MTD and observed over28 days, the most acutely toxic porphyrin was found to be devoid of toxicity, as measured by blood chemistrypanels. The remaining two less acutely toxic compounds both elicited significant changes, characterized bymoderate to severe thrombocytopenia, failure to gain weight normally and changes in liver enzymes indicativeof mild hepatotoxicity. All toxic effects were transient, with platelets rebounding to above normal levels atday 28. We conclude that thrombocytopenia is the dose limiting toxicity for boronated porphyrins in mammalsand suggest that these effects may be due to the porphyrin, not the borane or carborane.