1,2,5-硒二唑嘧啶衍生物ASPO的合成及抗氧化与抗肿瘤活性  

Synthesis,Antioxidant and Anticancer Activities of 1,2,5-Selenadiazole Pyrimidine Heterocyclic Derivative ASPO

作　　者：黄晓纯[1] 郑军生[2] 陈填烽[1] 张逸波[1] 罗懿[1] 郑文杰[1] 

机构地区：[1]暨南大学化学系,广州510632 [2]中山大学附属第三医院,广州510630

出　　处：《高等学校化学学报》2012年第5期976-982,共7页Chemical Journal of Chinese Universities

基　　金：教育部新世纪优秀人才支持计划(批准号:NCET 10-0119);国家自然科学基金(批准号:20901030;21071062);广东省科技攻关项目(批准号:2008A030201020)资助

摘　　要：合成了5-氨基-[1,2,5]硒二唑[3,4-d]嘧啶-7-酮(ASPO),研究了其抗氧化与抗肿瘤活性,并初步阐述了其作用机制.结果表明,ASPO具有良好的抗氧化活性,可抑制溶液中1,1-二苯基-2-苦基肼(DPPH)和2,2-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐(ABTS)自由基的形成,并呈剂量效应.此外,ASPO能有效抑制5种肿瘤细胞的生长,其中,A-375黑色素瘤细胞对ASPO具有良好的敏感性,其IC50值为14.1μg/mL.对作用机制的研究发现,ASPO处理可诱导肿瘤细胞中Sub-G1凋亡峰的累积、染色质固缩及凋亡小体的形成,说明诱导细胞凋亡是ASPO发挥抗肿瘤活性的主要机制.进一步利用光谱滴定和黏度实验研究了ASPO与CT-DNA的相互作用,发现ASPO以沟面结合方式与CT-DNA结合,表明ASPO可能通过与DNA相互作用而触发肿瘤细胞凋亡通路.The trace element selenium（Se） is an essential nutrient of fundamental importance to human and animal.Epidemiological,preclinical and clinical studies have supported the role of Se as potent cancer chemopreventive agents.Se-containing heterocyclic compounds have attracted more and more attention due to their anticancer potential and interesting chemical properties.In the present study,a selenadiazole pyrimidine heterocyclic derivative 5-amino-[1,2,5]selenadiazolo-[3,4-d]pyrimidin-7-ol（ASPO） was synthesized and characterized by ESI-MS,1H NMR,elemental analysis,IR,UV-Vis absorption spectroscopy and fluorescence spectroscopy.Its antioxidant and anticancer activities were evaluated.The results show that ASPO can effectively scavenge the 2,2′-azinobis-3-ethylbenzothiazolin-6-sulfonic acid（ABTS） and 1,1-diphenyl-2-picryhydrazyl（DPPH） free radicals in a dose-dependent manner,demonstrating its strong antioxidant activity.The in vitro anticancer activities of ASPO were screened by MTT assay against various cancer cell lines and it was found that ASPO could effectively inhibit cancer cell growth,especially A-375 human melanoma cells.Further investigation on the action mode show that ASPO induces Sub-G1 peak accumulation,chromatin condensation and the formation of apoptotic bodies in a dose-dependent manner in A-375 cells,indicating that apoptosis is the main mechanism accounting for the anticancer action of ASPO.Moreover,it was showed that ASPO could bind to CT-DNA by minor groove.The results support that ASPO induces cancer cell apoptosis through its interaction with DNA.

关 键 词：硒杂环衍生物 抗氧化活性 抗肿瘤活性 凋亡 DNA相互作用 

分 类 号：O627[理学—有机化学]