含1,2-苯并噻嗪结构的咪唑并［1,2-b］［1,3,4］三氮唑衍生物的合成及其抗肿瘤活性

Synthesis and antitumor activity of 1, 2-benzothiazines imidazolo ［1, 2-b］［1, 3, 4］ triazazole derivatives

摘要: 以吡罗昔康甲基物为原料，利用生物电子等排等药物设计原理，合成8个结构新颖的三氮唑化合物，其结构经¹H NMR、MS表征。通过测定对胰腺癌细胞Capan-1和白血病细胞L1210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 6b (IC₅₀=3.6±0.5 μmol/L)对胰腺癌细胞Capan-1表现出较好的抑制活性；化合物 6a (IC₅₀=1.8±0.2 μmol/L)对白血病细胞L1210表现出较好的抑制活性。初步的抗肿瘤活性实验结果表明，咪唑并三氮唑侧链的引入，对提高该类化合物的抗肿瘤活性有一定的作用。

Abstract: In this study, triazazole moiety was introduced to piroxicam, a nonsteroidal anti-inflammatory drug, via bioisosterism to produce eight target analogs, which were structurally characterized by ¹H NMR and MS. These target compounds were tested for inhibitory activities on pancreatic cancer cell(Capan-1)and leukemia cell(L1210). The results showed that compound 6b had good antiproliferative activity against Capan-1 cells(IC₅₀=3. 6±0. 5 μmol/L); while compound 6a had good antiproliferative activity against L1210 cells(IC₅₀=1. 8±0. 2 μmol/L), indicating that the introduction of the imidazolo［1, 2-b］［1, 3, 4］triazazole moiety could be helpful to improve the antitumor activity of these compounds.