Larsson B S, Larsson B, Roberto A
Department of Toxicology, Uppsala University, Sweden.
Pigment Cell Res. 1989 Jul-Aug;2(4):356-60. doi: 10.1111/j.1600-0749.1989.tb00220.x.
Previous studies have shown that some thioamides, e.g., thiouracil, are incorporated as false precursors into melanin during its synthesis. If boronated analogs of the thioamides share this property, the melanin of melanotic melanomas offers a possibility for specific tumoural uptake and retention of boron as a basis for neutron capture therapy. We report on the synthesis of boronated 1H-1,2,4-triazole-3-thiol (B-TZT), boronated 5-carboxy-2-thiouracil (B-CTU), and boronated 5-diethylaminomethyl-2-thiouracil (B-DEAMTU) and the localization of these substances in melanotic melanomas transplanted to mice. The distribution in the mice was studied by boron neutron capture radiography. B-TZT and B-CTU showed the highest tumour:normal tissue concentration ratios, with tumour:liver ratios of about 4 and tumour:muscle ratios of about 14; B-DEAMTU showed corresponding ratios of 1.4 and 5, respectively. The absolute concentration of boron in the tumours, however, was more than three times higher in the mice injected with B-TZT, compared with B-CTU. The results suggest that B-TZT may be the most promising compound of the three tested with regard to possible therapy of melanotic melanomas.
先前的研究表明，一些硫代酰胺，如硫脲嘧啶，在黑色素合成过程中作为假前体掺入黑色素中。如果硫代酰胺的硼化类似物具有这种特性，那么黑色素瘤的黑色素就为硼的特异性肿瘤摄取和保留提供了可能性，作为中子俘获疗法的基础。我们报道了硼化1H-1,2,4-三唑-3-硫醇（B-TZT）、硼化5-羧基-2-硫脲嘧啶（B-CTU）和硼化5-二乙氨基甲基-2-硫脲嘧啶（B-DEAMTU）的合成以及这些物质在移植到小鼠体内的黑色素瘤中的定位。通过硼中子俘获射线照相术研究了这些物质在小鼠体内的分布。B-TZT和B-CTU显示出最高的肿瘤与正常组织浓度比，肿瘤与肝脏的比值约为4，肿瘤与肌肉的比值约为14；B-DEAMTU的相应比值分别为1.4和5。然而，与B-CTU相比，注射B-TZT的小鼠肿瘤中硼的绝对浓度高出三倍多。结果表明，就黑色素瘤的可能治疗而言，B-TZT可能是三种受试化合物中最有前景的化合物。
