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

HAN Chun; WU Lintao; HU Xiaoqin; SUN Long; HUANG Zhangjian; ZHANG Yihua

doi:10.11665/j.issn.1000-5048.20180107

Journal of China Pharmaceutical University > 2018 > 49(1): 48-55. > DOI: 10.11665/j.issn.1000-5048.20180107

HAN Chun, WU Lintao, HU Xiaoqin, SUN Long, HUANG Zhangjian, ZHANG Yihua. Design, synthesis and anti-NSCLC activity of hybrids of anilinopyrimidines and diazeniumdiolates[J]. Journal of China Pharmaceutical University, 2018, 49(1): 48-55. DOI: 10.11665/j.issn.1000-5048.20180107

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

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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 (IC₅₀=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.
- anilinopyrimidines,
- diazeniumdiolates,
- epithelial growth factor receptor,
- gefitinib,
- synthesis,
- non-small cell lung cancer,
- antitumor activity

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