State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Chemical Engineering of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
Eur J Med Chem. 2013 Nov;69:508-20. doi: 10.1016/j.ejmech.2013.08.055. Epub 2013 Sep 17.
A series of novel thiourea α-aminophosphonate derivatives containing DHA structure was designed and synthesized as antitumor agents. Their inhibitory activities against the NCI-H460 (lung), A549 (lung adenocarcinoma), HepG2 (liver) and SKOV3 (ovarian) human cancer cell lines were estimated using MTT assay in vitro. The screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which indicated that the compound can induce cell apoptosis in A549 cells.
设计并合成了一系列含有 DHA 结构的新型硫脲 α-氨基膦酸酯衍生物作为抗肿瘤药物。采用 MTT 法体外评价了它们对 NCI-H460（肺癌）、A549（肺腺癌）、HepG2（肝癌）和 SKOV3（卵巢癌）人癌细胞系的抑制活性。筛选结果表明，许多化合物对测试的癌细胞系表现出中等至高强度的抗肿瘤活性，并且与商业抗癌药物 5-氟尿嘧啶相比，大多数化合物表现出更强的抑制活性。通过吖啶橙/溴化乙锭染色、Hoechst 33258 染色、JC-1 线粒体膜电位染色、TUNEL 检测、DNA 梯状电泳和流式细胞术初步研究了化合物 5f 的作用机制，表明该化合物能诱导 A549 细胞发生细胞凋亡。
