Centro de Química Medicinal da Universidade do Porto (CEQUIMED-UP), Rua Aníbal Cunha 164, 4050-047 Porto, Portugal.
Bioorg Med Chem. 2012 Jan 1;20(1):25-33. doi: 10.1016/j.bmc.2011.11.042. Epub 2011 Nov 30.
Thirty-one 2'-hydroxychalcones were prepared via solid-phase synthesis by base-catalyzed aldol condensation of substituted 2'-hydroxyacetophenones and benzaldehydes. Chalcones were tested for their growth inhibitory activity in three human tumor cell lines (MCF-7, NCI-H460 and A375-C5) using the SRB assay. Results revealed that several of the tested compounds caused a pronounced dose-dependent growth inhibitory effect on the tumor cell lines studied in the low micromolar range. To gain further insight on the cellular mechanism of action of this class of compounds, studies of their effect on cell cycle profile as well as on induction of cellular apoptosis were also carried out. Generally, the tested chalcones interfered with the cell cycle profile and increased the percentage of apoptotic MCF-7 cells. The results here presented may help to identify new chalcone-like structures with optimized cell growth inhibitory activity which may be further tested as potential antitumor agents.
通过碱催化取代的 2'-羟基苯乙酮和苯甲醛的Aldol 缩合反应，以固相合成的方式制备了 31 种 2'-羟基查耳酮。使用 SRB 测定法，在三种人肿瘤细胞系（MCF-7、NCI-H460 和 A375-C5）中测试查耳酮对生长的抑制活性。结果表明，在所研究的肿瘤细胞系中，几种测试化合物在低微摩尔范围内对细胞生长表现出明显的剂量依赖性抑制作用。为了进一步了解该类化合物的细胞作用机制，还研究了它们对细胞周期谱的影响以及诱导细胞凋亡的影响。一般来说，测试的查耳酮会干扰细胞周期谱并增加 MCF-7 细胞的凋亡百分比。这里呈现的结果可能有助于识别具有优化细胞生长抑制活性的新型查耳酮样结构，这些结构可以进一步作为潜在的抗肿瘤剂进行测试。
