Elo H, Mutikainen I, Alhonen-Hongisto L, Laine R, Jänne J
Department of Chemistry, University of Helsinki, Finland.
Cancer Lett. 1988 Jul;41(1):21-30. doi: 10.1016/0304-3835(88)90050-x.
Diethylglyoxal bis(guanylhydrazone) (DEGBG), a novel analog of the antileukemic agent methylglyoxal bis(guanylhydrazone) (MGBG) was synthesized. It was found to be the most powerful inhibitor of yeast S-adenosylmethionine decarboxylase (AdoMetDC) so far studied (Ki approx. 9 nM). This property, together with the finding that the compound is a weaker inhibitor of intestinal diamine oxidase than are MGBG and its glyoxal, ethylglyoxal and ethylmethylglyoxal analogs, makes the compound a promising candidate as a polyamine antimetabolite for chemotherapy studies. DEGBG was also found to potentiate the antiproliferative effect of the ornithine decarboxylase inhibitor alpha-difluoromethyl ornithine against mouse L1210 leukemia cells in vitro. DEGBG increased several-fold the intracellular putrescine concentration of cultured L1210 cells, just as MGBG and its ethylglyoxal analog are known to do. The results strongly suggest that DEGBG is worth further studies. Combined with previous studies, they also made possible the construction of some empirical rules concerning the structure-activity relationships of bis(guanylhydrazone) type inhibitors of AdoMetDC. The identity of DEGBG was confirmed by a single-crystal X-ray analysis and by 1H- and 13C-NMR spectroscopy. It consisted of the same isomer as MGBG and several of its analogs are known to consist of.
合成了二乙二醛双（胍腙）（DEGBG），它是抗白血病药物甲基乙二醛双（胍腙）（MGBG）的一种新型类似物。已发现它是迄今为止所研究的酵母S - 腺苷甲硫氨酸脱羧酶（AdoMetDC）最有效的抑制剂（Ki约为9 nM）。这一特性，再加上该化合物作为肠道二胺氧化酶抑制剂比MGBG及其乙二醛、乙醛和乙基甲基乙二醛类似物更弱这一发现，使得该化合物成为化疗研究中一种有前景的多胺抗代谢物候选药物。还发现DEGBG能增强鸟氨酸脱羧酶抑制剂α - 二氟甲基鸟氨酸对小鼠L1210白血病细胞的体外抗增殖作用。与MGBG及其乙醛类似物一样，DEGBG使培养的L1210细胞内的腐胺浓度增加了几倍。结果强烈表明DEGBG值得进一步研究。结合先前的研究，这些结果还使得构建一些关于AdoMetDC双（胍腙）型抑制剂构效关系的经验规则成为可能。通过单晶X射线分析以及1H - 和13C - NMR光谱证实了DEGBG的结构。它与MGBG具有相同的异构体，并且已知其几种类似物也由相同异构体组成。
