苯胺基嘧啶/偶氮鎓二醇盐杂合物的设计、合成及其抗非小细胞肺癌活性

Design,synthesis and anti-NSCLC activity of hybrids of anilinopyrimidines and diazeniumdiolates

为寻找活性强的抗非小细胞肺癌(NSCLC)药物,设计、合成了15个结构新颖的苯胺基嘧啶/偶氮鎓二醇盐杂合物9a^9e、10a^10e、11a^11e,采用MTT法考察其对表皮生长因子受体(EGFR)L858R/T790M突变的人肺腺癌细胞H1975的增殖抑制活性。结果表明,化合物9a^9e显著抑制H1975细胞的增殖,优于对照药吉非替尼(gefitinib)。其中,化合物9b活性最强(IC_(50)=0.65μmol/L)。分子对接提示,化合物9b可能通过氢键和静电作用力等与EGFR T790M活性部分结合,值得进一步研究。

To search for potent drugs against non-small-cell lung cancer(NSCLC),a series of hybrids(9a-9e,10a-10e and11a-11e)from anilinopyrimidines and diazeniumdiolates were designed and synthesized.The MTT assay was employed to evaluate their antiproliferative activity against H1975cells harboring epithelial growth factor receptor(EGFR)L858R/T790M mutation.The results showed that compounds9a-9e displayed remarkable inhibitory activity on H1975cells.Among these compounds,the most potent was compound9b(IC50=0.65μmol/L),which was superior to the positive control gefitinib.Additionally,molecular docking study indicated that9b could bind with EGFR T790M by forming hydrogen bond,electrostatic interactions,et al,suggesting that compound9b may be a potential anti-NSCLC agent for further investigation.