Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Bioorg Med Chem Lett. 2010 Jan 15;20(2):591-3. doi: 10.1016/j.bmcl.2009.11.083. Epub 2009 Nov 22.
The synthesis of several novel substituted (Z)-2-amino-5-(1-benzyl-1H-indol-3-yl)methylene-1-methyl-1H-imidazol-4(5H)-ones structurally related to aplysinopsin have been carried out under microwave irradiation and conventional heating methods. The analogs 3a, 3b, 3d-3g,3k and 3l were evaluated for their in vitro cytotoxic activity against an NCI 60 human tumor cell line panel. Compound 3f exhibited good growth inhibitory properties against all but four of the human cancer cell lines examined, and afforded LC(50) values <10microM for 30% of the cell lines in the panel. Compound 3e was an effective inhibitor of leukemia, CNS, melanoma, and breast cancer cell growth, but generally less effective as a cytotoxic agent. Thus, the aplysinopsin analog 3f was regarded as a useful lead compound for further structural optimization.
已经通过微波辐射和常规加热方法合成了几种新型取代的（Z）-2-氨基-5-（1-苄基-1H-吲哚-3-基）亚甲基-1-甲基-1H-咪唑-4（5H）-酮，这些化合物与阿普里辛类似物结构相关。对类似物 3a、3b、3d-3g、3k 和 3l 进行了体外细胞毒性活性评价，针对 NCI 60 种人类肿瘤细胞系进行了评价。化合物 3f 对除四种被检测的人类癌细胞系外的所有癌细胞系均表现出良好的生长抑制特性，并对该细胞系中的 30%提供了 LC(50)值<10μM。化合物 3e 是白血病、中枢神经系统、黑色素瘤和乳腺癌细胞生长的有效抑制剂，但作为细胞毒性剂的效果通常较差。因此，阿普里辛类似物 3f 被认为是进一步结构优化的有用先导化合物。
