Synthesis of Analogues of NSC73306 to Circumvent Multidrug Resistance in Cancer

合成 NSC73306 类似物以规避癌症的多药耐药性

• 批准号: 7968999
• 负责人: NICO TJANDRA
• 金额: $ 16.87万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7968999
• 关键词: ABCB1 gene; Acids; Annual Reports; Binding; Cells; Digestion; Human body; Isatin; Malignant Neoplasms; Mediating; Multi-Drug Resistance; P-Glycoprotein; P-Glycoproteins; Paper; Pharmaceutical Preparations; Precipitation; Proteins; Resistance; Sampling; Series; Structure; Students; Testing; alkalinity; analog; base; cancer cell; cytotoxic; experience; killings; liquid chromatography mass spectrometry

More recently with the help of a summer student (Jiayang Li), I have synthesized an additional twenty-three compounds based on our experiences with the first set and the commercial availability of intermediates. The p-dimethylamino substituted derivative was finally prepared after much labor and, as expected, found to be soluble in dilute acid, but as the sample was diluted even further for testing, precipitation occurred due to its weak basicity. Therefore a new synthesis involving the much more strongly basic p-dimethylaminomethyl derivative was developed and its synthesis is nearing completion. I also continue to examine the structures of related proteins in the GFP series by digestion and LC/MS (J.-R. Gillet). The synthesized compounds are being tested for its selectivity in killing cancer cells. In particular, cancel cells that are showing multidrug-resistance.

最近，在一名暑期学生（李佳阳）的帮助下，我根据第一组的经验和中间体的商业可用性，合成了另外23种化合物。经过大量劳动最终制备了对二甲氨基取代的衍生物，并且如预期的那样，发现其可溶于稀酸，但是当样品被进一步稀释以进行测试时，由于其弱碱性而发生沉淀。因此，开发了一种新的合成方法，包括更强碱性的对二甲氨基甲基衍生物，其合成接近完成。 我还继续通过消化和LC/MS检查GFP系列中相关蛋白质的结构（J. R. Gillet）。 合成的化合物正在测试其杀死癌细胞的选择性。特别是，消除显示多药耐药性的细胞。