含1,2-苯并噻嗪结构的杂原子取代薁类衍生物的合成及其抗肿瘤活性  

Synthesis and antitumor activity of heteroatom-substituted azulenes derivatives of 1,2-benzothiazine

作　　者：赵小美 王新 汲霞 张璟 张华 胡国强[2] ZHAO Xiaomei;WANG Xin;JI Xia;Zhang Jing;ZHANG Hua;HU Guoqiang(College of Pharmacy,Qilu Medical University,Zibo 255213;Institute of Pharmacy,Henan University,Kaifeng 475001,China)

机构地区：[1]齐鲁医药学院药学院,淄博255213 [2]河南大学药物研究所,开封475001

出　　处：《中国药科大学学报》2024年第5期634-638,共5页Journal of China Pharmaceutical University

基　　金：齐鲁医药学院科研团队支持计划;山东省卫生健康委员会医疗卫生科技项目(No.202202020715);山东省高校科研计划项目(J17KB091)。

摘　　要：以吡罗昔康甲基物为原料,利用生物电子等排和活性拼接等药物设计原理,设计并合成10个结构新颖的目标化合物,其结构经1H NMR、MS等表征。通过测定对胰腺癌细胞Capan-1、白血病细胞L1210和人肝癌细胞SMMC-7721的抑制活性,评价目标化合物的体外抗肿瘤活性。结果表明,化合物6f(IC_(50)=4.8±0.5μmol/L)对胰腺癌细胞Capan-1表现出较好的抑制活性;化合物6b(IC_(50)=2.6±0.3μmol/L)对白血病细胞L1210表现出较好的抑制活性;化合物6c(IC_(50)=2.1±0.2μmol/L)对人肝癌细胞SMMC-7721表现出较好的抑制活性。初步的抗肿瘤活性实验结果表明,薁类衍生物的引入,对提高该类化合物的抗肿瘤活性有一定的作用。Using methylated pyrroloxicam as a starting material and following the principles of drug design such as bioisosterism and active site binding,we designed and synthesized ten structurally novel target compounds,whose structures were characterized by 1H NMR and MS analysis.The in vitro antitumor activity of these title compounds was evaluated by measuring their inhibitory activity against pancreatic cancer cells Capan-1,leukemia cells L1210,and human liver cancer cells SMMC-7721.The results showed that compound 6f(IC_(50)=4.8±0.5μmol/L)exhibited good inhibitory activity against Capan-1 pancreatic cancer cells,that compound 6b(IC_(50)=2.6±0.3μmol/L)showed good inhibitory activity against L1210 leukemia cells,and that compound 6c(IC_(50)=2.1±0.2μmol/L)displayed good inhibitory activity against SMMC-7721 human liver cancer cells.These preliminary results from the antitumor activity experiments suggest that the introduction of benzothiazine derivatives plays a certain role in enhancing the antitumor activity of this class of compounds.

关 键 词：薁类衍生物 1 2-苯并噻嗪 合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]