新型有机锗倍半氧化物的合成及体外抑癌活性研究

Synthesis and cytotoxicity of novel organogermanium sesquioxides

目的合成更强抗癌活性的有机锗化合物,分析其分子结构和抗癌活性之间的关系。方法通过一系列化学反应合成了4种含氧芴酰胺或菲酯基团的新型有机锗倍半氧化物(4a,4b,5a,5b),用IR、1HNMR和元素分析确定它们的结构。用MTT方法检测4种化合物对人前列腺癌细胞(PC-3M)和人白血病癌细胞(K562)的抑制作用。结果 4a,4b,5a和5b对2种体外培养癌细胞均显示了较强的抑制作用,对PC-3M的IC_(50)分别为10.6,20.8,7.4和12.5μmol/L,对K562的IC_(50)分别为8.5,15.6,5.7和9.8μmol/L。对2种肿瘤细胞株,不含甲基基团的化合物(4a和5a)比含甲基的化合物(4b和5b)具有更强的抑癌活性(P<0.05);菲酯有机锗类化合物(5a和5b)的IC_(50)明显低于相应的氧芴酰胺有机锗类化合物(4a和4b)(P<0.05);化合物4a,4b和5b对K562的抑制作用明显高于PC-3M(P<0.05),化合物5a对2种肿瘤细胞株的抑制作用没有明显差异(P>0.05)。结论合成的新型有机锗倍半氧化物能够显著抑制体外培养癌细胞的增殖,研究结果对设计合成新型有机锗抗癌药物具有一定的指导意义。

Objective To synthesize novel organogermanium compounds with stronger cytotoxic activities,and study the relationship between the structure and anticancer activity. Methods Four novel organogermanium compounds with dibenzofuran or phenanthrene moiety were synthesized by a series of chemical reaction,and their structures were determined by IR,1HNMR,and elemental analysis. The cytotoxicities of the novel compounds against prostate cancer cells( PC-3M) and human chronic myeloid leukemia cells( K562) were measured by MTT assay. The experiments were repeated for three times. Results Four compounds( 4a,4b,5a,and 5b) presented strong anticancer activity against PC-3M and K562 cell lines. For PC-3M,IC_(50) was 10. 6,20. 8,7. 4 and 12. 5μmol/L,respectively. For K562 cells,IC_(50) was8. 5,15. 6,5. 7 and 9. 8μmol/L,respectively. The inhibition was not only aromatic chromophore moiety dependent,but also methyl substitution was related. The compounds without methyl group( 4a and 5a) shown stronger inhibition effect than those with methyl group( 4b and 5b)( P < 0. 05). The compounds with phenanthrene moiety( 5a and 5b) had lower IC_(50) values than those with dibenzofuran moiety( 4a and 4b)( P < 0. 05). Conclusion The anticancer activities of organogermanium compounds were enhanced obviously by the modification of the parent compound,Ge-132. These results offered a new important guidance for the design and synthesis of organogermanium compounds with stronger anticancer activities.