School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK; Faculty of Pharmacy, Zagazig University, Egypt.
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6886-9. doi: 10.1016/j.bmcl.2013.09.087. Epub 2013 Oct 6.
Series of substituted 4,6-diamino-1,3,5-triazine-2-carbohydrazides and -carboxamides have been synthesised, based on molecular modelling of candidate structures related to the previously reported Rad6B-inhibitory diamino-triazinylmethyl benzoate anticancer agents TZ8 and TZ9. Synthesis of the target compounds was readily accomplished in two steps from aryl biguanides via reaction of phenylhydrazine or benzylamines with key 4-amino-6-(arylamino)-1,3,5-triazine-2-carboxylate intermediates. These new triazine derivatives were tested for in vitro anticancer activity against the Rad6B expressing human breast cancer cell lines MDA-MB-231 and MCF-7. Active compounds, such as the triazinyl-carbohydrazides 3a-e, were found to exhibit low micromolar IC50 values particularly in the Rad6B-overexpressing MDA-MB-231 cell line.
已经合成了一系列取代的 4,6-二氨基-1,3,5-三嗪-2-碳酰肼和 -甲酰胺，这些化合物是基于与之前报道的 Rad6B 抑制性二氨基三嗪基甲基苯甲酸酯抗癌剂 TZ8 和 TZ9 相关的候选结构的分子建模。通过芳基双胍与关键的 4-氨基-6-(芳基氨基)-1,3,5-三嗪-2-羧酸酯中间体反应，很容易从芳基双胍出发两步合成目标化合物。这些新的三嗪衍生物在体外对表达 Rad6B 的人乳腺癌细胞系 MDA-MB-231 和 MCF-7 进行了抗癌活性测试。发现活性化合物，如三嗪基-碳酰肼 3a-e，在 Rad6B 过表达的 MDA-MB-231 细胞系中表现出低微摩尔 IC50 值。
