Synthesis of carboranes containing an azulene framework and in vitro evaluation as boron carriers
Synthesis of carboranes containing an azulene framework and in vitro evaluation as boron carriers
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DOI：
10.1021/jm970023x
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发表时间：
1997-08-29
影响因子：
7.3
通讯作者：
Yamamoto, Y
中科院分区：
文献类型：
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作者：
Nakamura, H;Sekido, M;Yamamoto, Y
通过钯催化 1-碳硼基三丁基锡烷 (4) 与甘菊醛 (3 和 9) 的加成反应合成 3-(0-碳硼基羟甲基)-7-异丙基薁磺酸钠 (1) 和 3-(邻碳硼基甲基)-7-异丙基薁磺酸钠 (2)。 1的水溶性约为10(-6)M，而2的水溶性约为10(-3)M，足以满足临床使用。 1对B-16黑色素瘤细胞的细胞毒性(IC50)约为10(-5)M，而2的细胞毒性约为10(-4)M。该值接近于临床使用的BPA(类似于9×10(-3)M)。 B-16细胞的硼摄取量为1个B/10(6)细胞0.17μg和2个B/10(6)细胞0.25μg。很明显，化合物2在B-16黑色素瘤细胞中以显着高的水平积累，尽管它是高度水溶性的并且其细胞毒性显着低。
3-(0-Carboranylhydroxymethyl)-7-isopropylazulene sodium carboxylate (1) and 3-(o-carboranylmethyl)-7-isopropylazulene sodium sulfonate (2) were synthesized from the palladium-catalyzed addition reaction of 1-carboranyltributylstannnane (4) to azulene aldehydes (3 and 9). Although the water solubility of 1 was of the order of 10(-6) M, that of 2 was bf the order of 10(-3) M and was enough for clinical use. The cytotoxicity of 1 (IC50) toward B-16 melanoma cells was of the order of 10(-5) M, whereas that of 2 was of the order of 10(-4) M. This value was close to that of BPA (similar to 9 x 10(-3) M) which is utilized for clinical use. The boron uptake by B-16 cells was 0.17 mu g of B/10(6) cells for 1 and 0.25 mu g of B/10(6) cells for 2. It is clear that compound 2 accumulates in B-16 melanoma cells with a significantly high level although it is highly water soluble and its cytotoxicity is significantly low.