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.
Nakamura
H
H
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai, Japan.
Sekido
M
M
Yamamoto
Y
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D052176:Azulenes; D001895:Boron / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D016754:Boron Neutron Capture Therapy; D002470:Cell Survival / Q000187:drug effects; D003508:Cycloheptanes / Q000737:chemistry*; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052176:Azulenes; D001896:Boron Compounds; D003508:Cycloheptanes; D003517:Cyclopentanes; D004337:Drug Carriers; C005525:azulene; D001895:Boron