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Synthesis of carboranes containing an azulene framework and in vitro evaluation as boron carriers.


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.