Nakamura H, Sekido M, Yamamoto Y
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai, Japan.
J Med Chem. 1997 Aug 29;40(18):2825-30. doi: 10.1021/jm970023x.
3-(o-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-carboranyltributylstannane (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 of 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 (approximately 9 x 10(-3) M) which is utilized for clinical use. The boron uptake by B-16 cells was 0.17 microgram of B/10(6) cells for 1 and 0.25 microgram 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.
3 - （邻 - 碳硼烷基羟甲基） - 7 - 异丙基薁羧酸钠（1）和3 - （邻 - 碳硼烷基甲基） - 7 - 异丙基薁磺酸钠（2）由1 - 碳硼烷基三丁基锡烷（4）与薁醛（3和9）的钯催化加成反应合成。尽管1的水溶性为10^(-6) M数量级，但2的水溶性为10^(-3) M数量级，足以用于临床。1对B - 16黑色素瘤细胞的细胞毒性（IC50）为10^(-5) M数量级，而2的为10^(-4) M数量级。该值与用于临床的双酚A（约9×10^(-3) M）接近。B - 16细胞对硼的摄取量对于1为0.17微克硼/10^6个细胞，对于2为0.25微克硼/10^6个细胞。很明显，化合物2尽管水溶性高且细胞毒性低，但仍能以显著高的水平在B - 16黑色素瘤细胞中积累。
