Chemistry Department, Ball State University, Muncie, IN 47306, USA.
Bioorg Med Chem. 2010 Mar 1;18(5):1899-909. doi: 10.1016/j.bmc.2010.01.037. Epub 2010 Jan 25.
A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2', C-3' and C-11' positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells.
通过短而高效的方法合成了一系列在 C-6、C-7 N、C-2'、C-3' 和 C-11' 位具有两个、三个或四个取代基的 lavendamycin 类似物,并将其评估为潜在的 NAD(P)H:醌氧化还原酶 (NQO1) 导向的抗肿瘤剂。这些化合物通过所需的 2-甲酰基喹啉-5,8-二酮与所需色氨酸的 Pictet-Spengler 缩合,然后进一步进行所需的转化来制备。代谢和毒性研究表明,与 NQO1 缺陷型肿瘤细胞相比,NQO1 最丰富的肿瘤细胞中,NQO1 的最佳底物也是最具选择性毒性的。