鬼臼毒素三氮唑衍生物的合成及其抗肿瘤活性  

Synthesis and anti-tumor activity of podophyllotoxin triazole derivatives

作　　者：赵明 郑奕[2] 孙淑霞[2] 毕文超[3] 陈虹[4] 

机构地区：[1]武警河南总队驻马店市支队卫生队,河南驻马店463000 [2]河南省驻马店市卫生学校,河南驻马店463000 [3]武警山东总队医院,山东济南250000 [4]武警后勤学院预防医学系生药学与药剂学教研室,天津300162

出　　处：《武警后勤学院学报（医学版）》2013年第7期606-608,共3页Journal of Logistics University of PAP（Medical Sciences）

摘　　要：【目的】获得更为高效的生物活性且具有抗多药耐药作用的合成抗肿瘤新化合物。【方法】将4β-叠氮-4-脱氧-4'-去甲基表鬼臼毒素与炔类化合物发生1,3-偶极环加成反应,合成了6个新型鬼臼毒素三氮唑衍生物,其结构经1H-NMR,TOF-MS证实。用磺酰罗丹明B比色法(sulforhodamine B colorimetric method,SRB法)筛选上述衍生物对K562,K562/A02细胞的体外抗肿瘤活性,经3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐比色法(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric method,MTT法)筛选了这些衍生物对KB和KBV细胞的体外抗肿瘤活性。【结果】6个化合物均为新化合物,其中4a,4b,4c,4d,4e和4f对K562/A02细胞的抗多药耐药活性显著高于VP-16,并且4a,4b,4e和4f对KBV细胞的抗多药耐药活性显著高于VP-16。【结论】新型鬼臼毒素衍生物具有较高的抗肿瘤活性和抗多药耐药性。[ Objective ] To synthetize anti-tumor compounds with superior bioactivity and anti-multidrug resistance. [ Methods ] Six novel derivatives of podophyllotoxin triazole have been synthesized by 1, 3-dipolar cycloaddition of 4/3 -azido-4^1-O-demethylpodophyllotoxin to alkynes. Their structures were conformed by 1H-NMR, TOF-MS. The anti-tumor activity of the derivatives was tested against K562 and K562/A02 by Sulforhodamine B colorimetric method in vitro, KB and KBV by 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyhetrazolium bro- mide colorimetric method in vitro. [Results] All the 6 derivatives were not reported before. The compounds 4a, 4b, 4c, 4d, 4e and 4f showed higher activity of anti-tumor muhidrug resistance as compared with VP-16 against K562/A02 in vitro. The compounds 4a, 4b, 4e and 4f showed higher activity of anti-tumor multidrug resistance as compared with VP-16 against KBV in vitro. [ Conclusion ] The results indicate that these compounds showed high anti-tumor activity and the activity of anti-tumor muhidrug resistance.

关 键 词：鬼臼毒素衍生物 化学合成 抗肿瘤 多药耐药 

分 类 号：R914[医药卫生—药物化学]