3-烟酰胺基-1,2,4-苯并三嗪-1,4-二氮氧化物的合成及体外抗肿瘤活性的测定

Synthesis of 3-Nicotinamide-1,2,4-Benzotriazine-1,4-Dioxide and the Determination of Its Anti-Tumor Activity in Vitro

目的合成3-烟酰胺基-1,2,4-苯并三嗪-1,4-二氮氧化物;测定3-烟酰胺基-1,2,4-苯并三嗪-1,4-二氮氧化物体外抗肿瘤活性。方法以苯并呋咱氮氧化物(BFO)和氨基氰为起始原料合成中间体3-氨基-1,2,4-苯并三嗪-1,4-二氮氧化物,所得的中间体和烟酰氯反应得目标化合物。以人乳腺癌MCF-7细胞、人肝癌HepG2细胞为模型,采用MTT分析法,测定3-烟酰胺基-1,2,4-苯并三嗪-1,4-二氮氧化物体外抗肿瘤活性。结果所合成的目标化合物经氢谱(1H-NMR)、质谱(MS)和红外光谱(IR)确证,纯度经HPLC检测达99.24%。结论合成了3-烟酰胺基-1,2,4-苯并三嗪-1,4-二氮氧化物;3-烟酰胺基-1,2,4-苯并三嗪-1,4-二氮氧化物对人乳腺癌MCF-7细胞、人肝癌HepG2细胞的活性大于替拉扎明。

OBJECTIVE To synthesize 3-nicotinamide-1,2,4-benzotriazine-1,4-dioxide and to determine its anti-tumor activity in vitro.METHODS Cyanogenamide and benzofuroxan were used as starting materials to prepare the intermediate（3-amino-1,2,4-benzotriazine-1,4-dioxide,Tirapazamine）.The objective substance was obtained from the reaction of the intermediate and nicotinic acyl chloride.The in vitro antitumor activities of the synthesized compounds were determined by MTT method using MCF-7 and HepG2 cells.RESULTS The obtained compounds were identified by 1H-NMR,MS and IR.The purity of the objective substance determined by HPLC was 99.24%.CONCLUSION The anti-tumor activity of 3-nicotinamide-1,2,4-benzotriazine-1,4-dioxide is much better than tirapazamine.