新型8-氨基喹啉-蛋氨酸衍生物合钌金属药物的合成和细胞毒活性及其与DNA相互作用研究  

A Novel Ru Metal Drugs of 8-Aminoquinoline-methionine Derivatives:Synthesis and Cytotoxicity with Reactivity Towards DNA

作　　者：干宁[1] 葛从辛[1] 王志颖[1] 余杨峰[1] 陆敏娟[1] 

机构地区：[1]宁波大学材化学院

出　　处：《中国药学杂志》2007年第19期1508-1512,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(No.20070243);浙江省自然科学基金资助项目(Y106725);浙江省科技攻关项目(No.2006C31040);浙江省教育厅基金(20061697);宁波市自然科学基金(No2006A610048)资助项目

摘　　要：目的设计并合成高效新型的钌配合物抗肿瘤药物。方法合成L-蛋氨酸酰-(8-喹啉基)胺(MHQA)和N-叔丁氧羰基MHQA缬氨酸酰-(8-喹啉基)胺(TMHQA),以这两种配体为基础合成了Ru(Ⅲ)配合物Ru(MHQA)和Ru(TMHQA)。用元素分析、质谱、红外光谱和核磁共振谱表征和推测两种配合物的结构。针对小鼠白血病细胞(P-388)、人急性早幼粒细胞性白血病细胞(HL-60)、人非小细胞性肺癌细胞(A-549)和人肝癌细胞(BEL-7402)测试了配体及其Ru(Ⅲ)配合物的体外细胞毒活性。结果该类Ru配合物在一定浓度下(1×10-6mol.L-1)对不同肿瘤细胞都有很高的抑制活性,且比相应配体显著增强。结论Ru(MHQA)和Ru(TMHQA)配合物具有显著抗肿瘤活性,期望将来从该类配合物中发现生物活性更突出的药物。OBJECTIVE To design and synthesize novel Ru complexes with activity. METHODS Two Ru complexes Ru （ MHQA）, Ru （TMHQA） were synthesized respectively with ligands L-methionine hydrazide- （8-quinolyl） amine （ MHQA ） and N-tert- butoxy carbonyl -L-methionine hydrazide-（8-quinolyl） amine（TMHQA）. The ligands were fully characterized by elemental analysis, infrared spectra,ESIMS and ^1H-NMR. The molecular structures of the complexes were deduced based on the ESIMS results. Finally, cytotoxicity activity of two ligands and their complex against P-388, HL-60, A-549 and BEL-7402 cell lines was studied in vitro. RE- SULTS The complexes exhibited high activity at the concentration of 1 × 10^-6mol·L^-1. The activity of complexes were absolutely greater than that of free ligands. CONCLUSION This new series of complexes show promising antitumor properties and are suitable for further development.

关 键 词：钌配合物 合成 抗肿瘤活性 8-氨基喹啉-蛋氨酸衍生物 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]