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New carborane‐based compounds for boron neutron capture therapybinding and toxicity of ANC‐1, DAC‐1 and B‐Et‐11‐OMe in cultured human glioma and mouse melanoma cells

 

作者: Peter Lindström,   Pär Olsson,   Jonas Malmqvist,   Jean Pettersson,   Peter Lemmen,   Birgit Werner,   Stefan Sjöberg,   Ake Olin,   Jörgen Carlsson,  

 

期刊: Anti-Cancer Drugs  (OVID Available online 1994)
卷期: Volume 5, issue 1  

页码: 43-52

 

ISSN:0959-4973

 

年代: 1994

 

出版商: OVID

 

关键词: Amino-carboranes;ANC-1;B-Et-11-OMe;boron neutron capture therapy;BSH;carborane;cellular binding;cellular toxicity;cultured cells;DAC-1;glioma;growth curve;ICP–AES;ICP–MS;melanoma

 

数据来源: OVID

 

摘要:

The toxicity and binding of the three new carborane based compounds: 2 (1,2-dicarba-closo-dodecaborane (12)-1(-yl-methoxy)-2-(3-amino-propyl))-1,3-propanedlol, called DAC-1; 7-(3-amino-propyl)-7,8-dicarba-nido-undecarborate (-1) called ANC-1; and rac-1-(9–0-carboranyl)-nonyl-2-methyl-glycero-3-phosphocholine, called B-Et-11-OMe, were analyzed with cultured human glloma cells, U-343MGa, and mouse melanoma cells, B16, as biological models. The prevlously developed compound di-sodium undecahydro-mercapto-closo-dodecarborate (BSH), which is tested for therapy of mallgnant gllomas, was analyzed for comparison. In the toxicity tests the cells were exposed to the substances at cell culture medium concentrations in the range 0–50 ppm boron for 1 or 20 h and thereafter analyzed regarding growth. Growth-disturbing effects were seen for the two compounds DAC-1 and B-Et-11-OMe at the concentrations corresponding to 15 and 50 ppm boron, respectively. The compounds ANC-1 and BSH showed no growth-disturbing effects at the tested concentrations. In the binding tests, the cells were Incubated for 20 h at about the highest compound concentrations that did not cause growth disturbances. The boron content in the cells was then determined by inductively coupled plasma–atomic emlssion spectrometry (ICP–AES) and in some cases ICP–mass spectrometry (ICP–MS). The most extensive binding was seen for DAC-1 and B-Et-11-OMe, which accumulated boron to about 100 and 60 times, respectively, compared with the concentration in the culture medium. The compound ANC-1 also accumulated boron in the cells but the boron could be easily washed out indicating no or only a weak binding. BSH did not accumulate. Further analysis should be made regarding blological properties such as intracellular compartmentallzation, metabolic interference and tumor specificity of the compounds DAC-1 and B-Et-11-OMe.

 

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