Synthesis, toxicity and biodistribution of two 5,15-di[3,5-(nido-carboranylmethyl)phenyl]porphyrins in EMT-6 tumor bearing mice.
Synthesis, toxicity and biodistribution of two 5,15-di[3,5-(nido-carboranylmethyl)phenyl]porphyrins in EMT-6 tumor bearing mice.
复制标题
两种 5,15-二[3,5-(nido-carboranylmethyl)苯基]卟啉在 EMT-6 荷瘤小鼠体内的合成、毒性和生物分布。
DOI：
10.1016/s0968-0896(03)00240-2
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发表时间：
2003
影响因子：
3.5
通讯作者：
Miura,Michiko
中科院分区：
文献类型：
--
作者：
Vicente,MGraçaH;Wickramasinghe,Anura;Nurco,DanielJ;Wang,HongJH;Nawrocky,MartaM;Makar,MichaelS;Miura,Michiko
报道了5，15-二[3，5-（邻碳硼烷甲基）苯基]卟啉5及其锌（Ⅱ）配合物6和相应的巢状碳硼烷卟啉7和8的全合成。卟啉6和钾nido-carborane的分子结构，并得到描述。本文报道了巢式碳卟啉7和巢式碳卟啉8在荷EMT-6乳腺癌BALB/c小鼠体内的分布。两种化合物都是有效的肿瘤定位剂，并向肿瘤递送治疗浓度的硼（平均值±标准差）：在3次注射总硼剂量为23 mg/kg体重的最后一次后2天，分别为32.5±7.1和54.3±14 μg/g，持续7和8天。发现锌（II）络合物8向肿瘤递送的硼的量是7的1.2-1.7倍，具有较低的肿瘤-血液硼浓度比（注射后2天，7和8分别为9.8/1和4.7/1）。给药后2天，两种卟啉的肿瘤与脑硼浓度比>100/1。巢式碳硼烷卟啉7和8在所用浓度下耐受良好（分别为75和78 mg/kg体重），在这些研究中未观察到发病率或死亡率。
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 μg/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.