Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570006, India.
Recent Pat Anticancer Drug Discov. 2011 May;6(2):186-95. doi: 10.2174/157489211795328459.
In search of synthetic chemotherapeutic substances capable of inhibiting, retarding, or reversing the process of multistage carcinogenesis, we synthesised a series of novel 1-(4-methoxybenzyl)-3-cyclopropyl-1H-pyrazol-5-amine derivatives 9(a-h) by a nucleophilic substitution reaction and characterized by (1)H and (13)C nuclear magnetic resonance (NMR), liquid chromatography mass spectrometry (LC/MS), Fourier-transform infrared (FTIR), and elemental analysis. These novel compounds were evaluated for their efficacy in inhibiting VERO normal and MCF-7 breast cancer cells proliferation by trypan blue exclusion assay, MTT assay, [(3)H] thymidine incorporation assay and DNA fragmentation analysis. Among the series, some compounds exhibited interesting growth inhibitory effects against cell lines. From the Structure-Activity Relationship studies, it has been revealed that, both novel patented compounds and therapeutic protocols of N-terminal pyrazole ring structures play key role in the antiproliferative activity.
为了寻找能够抑制、延缓或逆转多阶段致癌过程的合成化疗物质,我们通过亲核取代反应合成了一系列新型的 1-(4-甲氧基苄基)-3-环丙基-1H-吡唑-5-胺衍生物 9(a-h),并通过 (1)H 和 (13)C 核磁共振 (NMR)、液相色谱质谱联用 (LC/MS)、傅里叶变换红外 (FTIR) 和元素分析进行了表征。通过台盼蓝排斥试验、MTT 试验、[(3)H]胸苷掺入试验和 DNA 片段化分析,评估了这些新型化合物对 VERO 正常和 MCF-7 乳腺癌细胞增殖的抑制作用。在该系列中,一些化合物对细胞系表现出有趣的生长抑制作用。从构效关系研究中可以看出,新型专利化合物和 N-端吡唑环结构的治疗方案都在抗增殖活性中起着关键作用。