摘要
目的发现1,2-苯并噻嗪类抗肿瘤先导化合物,并研究其抗肿瘤活性。方法以吡罗昔康合成过程中的重要的中间体(CAS:35511-15-0)为原料,利用活性拼接原理,合成目标化合物,并通过核磁共振(NMR)、质谱(MS)、元素分析等方法对其结构进行表征;采用MTT法测定对胰腺癌细胞Capan-1、白血病细胞L1210和人肝癌细胞SMMC-7721的抑制活性,从而评价其体外抗肿瘤活性。结果化合物5c[IC50=(3.8±0.5)μmol·L^(-1)]对胰腺癌细胞Capan-1表现出较好的抑制活性;化合物5i[IC50=(1.8±0.3)μmol·L^(-1)]对白血病细胞L1210表现出较好的抑制活性;化合物5j[IC50=(2.9±0.3)μmol·L^(-1)]对人肝癌细胞SMMC-7721表现出较好的抑制活性。结论初步的抗肿瘤活性实验结果表明,三氮唑并噻二唑侧链的引入,对提高该类化合物的抗肿瘤活性有一定的作用。
OBJECTIVE To discover novel antitumor lead compounds derived from 1,2-benzothiazine and investigate their antitumor activities.METHODS The target compounds were designed and synthesized from 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide(key intermediate in the synthesis of piroxicam)based on the principle of splicing active substructures.Their structures were characterized by 1H-NMR,MS spectra and elemental analysis.The target compounds were screened for their antitumor potential by MTT.The in vitro antitumor activity of these compounds was evaluated on pancreatic cancer cell line Capan-1,leukemia cell line L1210 and human hepatoma cell line SMMC-7721,respectively.RESULTS Among these compounds,5c exhibited better inhibitory activity on pancreatic cancer cell Capan-1[IC50=(3.8±0.5)μmol·L^(-1)];5i showed better inhibitory activity on leukemia cell L1210[IC50=(1.8±0.3)μmol·L^(-1)];5j showed better inhibitory activity on human hepatoma cell SMMC-7721[IC50=(2.9±0.3)μmol·L^(-1)].CONCLUSION The preliminary results suggest that the introduction of triazolothiadiazole side chain could improve the antitumor activity of these compounds.
作者
赵小美
王新
张华
汲霞
张平平
胡国强
ZHAO Xiao-mei;WANG Xin;ZHANG Hua;JI Xia;ZHANG Ping-ping;HU Guo-qiang(College of Pharmacy,Qilu Medical University,Zibo 255213,China;Institute of Pharmacy,Henan University,Kaifeng 475001,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2023年第16期1457-1460,共4页
Chinese Pharmaceutical Journal
基金
山东省高校科研计划项目(科技类)资助(J18KB122)
齐鲁医药学院应用药学科研创新平台项目资助(2018ZBXC423)。
