School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
Eur J Med Chem. 2013 Oct;68:103-10. doi: 10.1016/j.ejmech.2013.07.014. Epub 2013 Aug 8.
A series of polyoxygenated cinnamoylcoumarins was synthesized as conformationally constrained analogs of cytotoxic diarylpentanoids. The title compounds were tested against the viability of human chronic myelogenous leukemia (K562), human acute lymphoblastic leukemia (MOLT-4) and human breast adenocarcinoma (MCF-7) cell lines by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Among them, all 6- or 7-hydroxylated compounds 6a-h exhibited remarkable cytotoxic activity. Particularly, 7-hydroxycoumarin analog 6h showed good antiproliferative activity against all tested cell lines (IC50 values≤5.5 μM). The preliminary study with selected compounds 6e and 6f showed that reactivity towards mitochondrial thiol compounds cab be considered as cytotoxic mechanism of designed compounds. Furthermore, the antioxidant activity evaluation of synthesized compounds showed that hydroxylated compounds had antioxidative potential at higher concentrations.
一系列多氧化肉桂酰香豆素被合成作为细胞毒性二芳基戊烷的构象限制类似物。通过 MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）测定法，用这些标题化合物测试了它们对人慢性髓性白血病（K562）、人急性淋巴细胞白血病（MOLT-4）和人乳腺癌（MCF-7）细胞系的活力。其中，所有 6-或 7-羟基化化合物 6a-h 表现出显著的细胞毒性活性。特别是 7-羟基香豆素类似物 6h 对所有测试的细胞系均表现出良好的抗增殖活性（IC50 值≤5.5 μM）。对选定的化合物 6e 和 6f 的初步研究表明，对线粒体硫醇化合物的反应性可被认为是设计化合物的细胞毒性机制。此外，合成化合物的抗氧化活性评估表明，羟基化化合物在较高浓度下具有抗氧化潜力。
