Manning H W, Cameron L M, LaFrance R J, Vaughan K, Rajaraman R
Department of Chemistry, Saint Mary's University, Halifax, Nova Scotia, Canada.
Anticancer Drug Des. 1985 Oct;1(1):37-43.
N,N-Bis-[(1-aryl-3-methyltriazen-3-yl)-methyl]-methylamines, 'bistriazenes', have anti-tumour activity against the TLX5 and PC6 mouse tumours and inhibit the growth of tumour cells growing in culture, without metabolic activation. The biological activity of the bistriazene appears to derive from facile hydrolysis to the cytotoxic monomethyltriazene, Ar-N = N-NHMe, and it is suggested that the bistriazene may be a good prodrug from for the 'active' metabolite of the anti-tumour dimethyltriazene, Ar-N-N = N-NME2. A kinetic study of the bistriazene hydrolysis shows that the reaction is retarded by electron-withdrawing substituents in the aryl group. The results can be interpreted by a mechanism in which the bistriazene behaves as an 'animal' (i.e. N-CH2-N) and undergoes anchimerically assisted fragmentation, via an iminium ion intermediate, to the monomethyltriazene.
N,N-双-[(1-芳基-3-甲基三氮烯-3-基)-甲基]-甲胺，即“双三氮烯”，对TLX5和PC6小鼠肿瘤具有抗肿瘤活性，并且在无代谢活化的情况下能抑制培养中的肿瘤细胞生长。双三氮烯的生物活性似乎源于其易水解为细胞毒性的单甲基三氮烯（Ar-N = N-NHMe），有人认为双三氮烯可能是抗肿瘤二甲基三氮烯（Ar-N-N = N-NMe2）的“活性”代谢物的良好前药。对双三氮烯水解的动力学研究表明，芳基中的吸电子取代基会阻碍该反应。这些结果可以通过一种机制来解释，即双三氮烯表现为一个“类胺”（即N-CH2-N），并通过亚胺离子中间体进行邻基参与辅助断裂，生成单甲基三氮烯。
