Abstract:
To search for potent drugs against non-small-cell lung cancer(NSCLC), a series of hybrids(
9a -
9e ,
10a -
10e and
11a -
11e) from anilinopyrimidines and diazeniumdiolates were designed and synthesized. The MTT assay was employed to evaluate their antiproliferative activity against H1975 cells harboring epithelial growth factor receptor(EGFR)L858R/T790M mutation. The results showed that compounds
9a -
9e displayed remarkable inhibitory activity on H1975 cells. Among these compounds, the most potent was compound
9b (IC
50=0. 65 μmol/L), which was superior to the positive control gefitinib. Additionally, molecular docking study indicated that
9b could bind with EGFR T790M by forming hydrogen bond, electrostatic interactions, et al, suggesting that compound
9b may be a potential anti-NSCLC agent for further investigation.