Structure-based design of nitrosoureas containing tyrosine derivatives as potential antimelanoma agents
Structure-based design of nitrosoureas containing tyrosine derivatives as potential antimelanoma agents
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DOI：
10.1016/s0223-5234(02)01343-0
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发表时间：
2002-04-01
影响因子：
6.7
通讯作者：
Gadjeva, V
中科院分区：
文献类型：
--
作者：
Gadjeva, V
两种新的亚硝基脲（TNUs）。合成了含有酪氨酸衍生物作为亚硝基脲细胞毒性基团载体的化合物。理化性质，如半衰期（tau（0.5））。测定烷基化和氨基甲酰基化活性。亚硝基脲对蘑菇酪氨酸酶的DOPA氧化酶活性的抑制作用强于抗肿瘤药物N '-环己基-N-（2-氯乙基）-N-亚硝基脲（洛莫司汀，CCNU）。研究了新合成的含酪氨酸的亚硝基脲的体外细胞毒性作用，并与CCNU进行了比较。与CCNU相比，含酪氨酸的亚硝基脲对B16黑色素瘤细胞的细胞毒性高于对YAC-1和对淋巴细胞的细胞毒性。基于上述结果，我们认为合成选择性更高、毒性更低的亚硝基脲衍生物是一个新的发展趋势。(C)2002年，Elsevier SAS科学与医学版。All rights reserved.
Two new nitrosoureas (TNUs). containing tyrosine derivatives as carriers of nitrosourea cytotoxic group hake been synthesised. The physicochemical properties such as half-life time (tau(0.5)). alkylating and carbamoylating activities were determined. The nitrosoureas showed a higher inhibiting effect on the DOPA-oxidase activity of mushroom tyrosinase than that of the antitumour drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU). In vitro cytotoxic effects of newly synthesised tyrosine containing nitrosoureas have been studied and compared to those of CCNU. A higher cytotoxicity to B16 melanoma cells than to YAC-1 and to lymphocytes was demonstrated for the tyrosine containing nitrosoureas in comparison with CCNU. Based on the results presented, we accept that a new trend for synthesis of more selective and less toxic nitrosourea derivatives as potential antimelanomic drugs might be developed. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.