摘要
目的:设计并合成新的3,5-二溴水杨醛缩-4-氨基安替比林席夫碱Cu(Ⅱ)配合物([CuL_(2)]),并评价其抗癌活性。方法:利用3,5-二溴水杨醛与4-氨基安替比林发生缩合反应,合成新的3,5-二溴水杨醛缩-4-氨基安替比林席夫碱配体(HL)。将HL与Cu(Ac)_(2)·H_(2)O通过溶剂热法合成了[CuL_(2)],并利用X射线单晶衍射、多晶粉末衍射(PXRD)、红外光谱(FT-IR)和热重分析(TGA-DSC)等技术对[CuL_(2)]进行表征。MTT法检测HL及[CuL_(2)]对MDA-MB-231细胞、SMMC-7721细胞、CNE-2Z细胞和A-549细胞的体外抗肿瘤活性。流式细胞术(FCM)分析[CuL_(2)]对MDA-MB-231细胞凋亡和周期的影响。结果:X射线单晶衍射分析显示,[CuL_(2)]为单核金属配合物,属单斜晶系,空间群为C 2/c,具有微扭曲的四方形配位结构;PXRD显示,[CuL_(2)]结晶度良好,晶体结构符合单晶测试的分析结果;配体和配合物的FT-IR特征峰与分子结构一致;TGA-DSC显示,[CuL_(2)]在270℃以下具有良好的热稳定性。MTT实验结果显示,当HL与Cu(Ⅱ)形成配合物时,[CuL_(2)]抗癌活性优于HL,其抑制MDA-MB-231细胞和SMMC-7721细胞活性较强,略低于顺铂。FCM分析结果显示,[CuL_(2)]可诱导MDA-MB-231细胞凋亡(P<0.05);[CuL_(2)]诱导MDA-MB-231细胞阻滞在G_(0)/G_(1)期和S期(P<0.05)。结论:合成得到[CuL_(2)],其可抑制MDA-MB-231细胞和SMMC-7721细胞活性,诱导MDA-MB-231细胞凋亡和细胞周期阻滞。
Objective:To design and synthesize a novel Cu(Ⅱ)complex based on 3,5-dibromosalicylaldehyde-4-aminoantipyrine Schiff base([CuL_(2)]),and evaluate its anticancer activity.Methods:A novel Schiff base ligand,3,5-dibromosalicylalde-4-aminoantipyrine(HL),was synthesized by condensation reaction of 3,5-dibromosalicylalde and 4-aminoantipyrine.The[CuL_(2)]was synthesized by solvothermal method with HL and Cu(Ac)_(2)·H_(2)O.The[CuL_(2)]was characterized by X-ray single crystal diffraction,polycrystaline powder X-ray diffraction(PXRD),Fourier transform infrared spectroscopy(FT-IR)and thermogravimetric analysis(TGA-DSC).The in vitro anticancer activity of HL and[CuL_(2)]on MDA-MB-231,SMMC-7721,CNE-2Z and A-549 cells was determined by MTT assay.The effect of[CuL_(2)]on apoptosis and cell cycle of MDA-MB-231 cells was analyzed by flow cytometry(FCM).Results:X-ray single crystal diffraction analysis showed that[CuL_(2)]was a mononuclear metal complex,belonging to the monoclinic crystal system,with space group of C 2/c and 4-coordination micro-torsion square structure;PXRD showed that the crystallinity of[CuL_(2)]was good,and the crystal structure accorded with the results of single crystal test;the FT-IR characteristic peaks were consistent with the molecular structures of ligand and complex;TGA-DSC analysis showed that[CuL_(2)]had good thermal stability below 270℃.The MTT assay results showed that when HL forms a complex with Cu(Ⅱ),[CuL_(2)]had better anticancer activity than HL,and its inhibitory activity on MDA-MB-231 cells and SMMC-7721 cells was stronger,which was slightly lower than that of cisplatin.The FCM analysis results showed that[CuL_(2)]could induce apoptosis in MDA-MB-231 cells(P<0.05),and induce cell cycle arrest in G_(0)/G_(1)and S phases in MDA-MB-231 cells(P<0.05).Conclusions:The[CuL_(2)]is synthesized,which can inhibit the activity of MDA-MB-231 and SMMC-7721 cells,and induce cell cycle arrest and apoptosis in MDA-MB-231 cells.
作者
陈司燮阳
李茹
柴俊
张涤清
殷华军
陈莎莉
胡静
CHEN Si-xie-yang;LI Ru;CHAI Jun;ZHANG Di-qing;YIN Hua-jun;CHEN Sha-li;HU Jing(School of Life Science,Bengbu Medical College,Bengbu Anhui 233030,China;School of Public Base,Bengbu Medical College,Bengbu Anhui 233030,China;School of Clinical Medicine,Bengbu Medical College,Bengbu Anhui 233030,China)
出处
《蚌埠医学院学报》
CAS
2023年第8期1080-1084,1089,共6页
Journal of Bengbu Medical College
基金
安徽省高校自然科学研究重点项目(2022AH051442)
国家级大学生创新创业训练计划项目(202210367008)。
