含喹啉基团的有机锗倍半氧化物的合成及对体外培养癌细胞的作用

目的合成新型有机锗喹啉酯倍半氧化物,研究它们对体外培养PC-3M细胞的抑制作用,分析作用机理,研究分子结构和抗癌活性之间的关系。方法利用氧化还原、加成、酰化、水解等反应合成了2种新型有机锗喹啉酯化合物。用MTT方法研究化合物分别在10μM,30μM和60μM对PC-3M癌细胞的抑制作用。显微镜下观察药物作用后的PC-3M细胞形态,应用流式细胞光度术检测药物对PC-3M细胞周期的影响。结果2种化合物对PC-3M的IC50分别为10μM和30μM;10～30μM浓度的药物能使细胞皱缩,碎片增加,药物不仅强烈抑制了细胞的增值,而且对细胞形态也产生了严重影响。细胞生长过程中,G0/G1和G2/M期细胞数量减少而S期细胞数量明显增多。结论合成的新化合物对体外培养PC-3M癌细胞的增殖具有很强的抑制作用,药物与细胞核内DNA发生了相互作用。化合物中甲基的存在不利于抗癌作用的发挥。

The Synthesis and Cytotoxic Activity of Novel Organogermanium Sesquioxides with Quinoline Moiety

Objective To synthesize new organogermanium compounds with stronger cytotoxic activities, and study the relationship between the structure and anticancer activity.Methods Two novel organogermanium sesquioxides with quinoline moiety were synthesized by a new method. Cell growth inhibition was measured by the MTT method. PC-3M prostate cancer cell line was treated with newly synthesized compounds. at 10 μm, 30 μm and 60 μm, respectively. The experiments were repeated three times.Results The IC50 of compounds were l0μm and 30μM, respectively. Cell morphology studies indicate that 10-30μM can cause cell irregularity, shrinking, and even fragmentation. Flow cytometeric data showed that the cell number in G0/G1 and G2/M phase was decreased but increased dramatically in S phase in the presence of the compounds.Conclusion The novel compounds exhibited stronger cytotoxic activities. DNA may be the primary target for the newly synthesized Ge132-quinoline compounds.