Design, Synthesis and Anti-NSCLC Activity of Hybrids of Anilinopyrimidines and Cinnamic Acids / 中国药学杂志

OBJECTIVE: To design and synthesize a series of hybrids of anilinopyrimidines and cinnamic acids and to find powerful anti-non-small cell lung cancer(NSCLC) drug. METHODS: Compounds 3a-3k were synthesized by combining anilinopyrimidines scaffolds and cinnamic acid derivatives through amide bonds, then the anti-NSCLS activity of these compounds was studied by MTT. RESULTS: Their structures were confirmed by MS and 1H-NMR. Most of target compounds displayed higher anti-proliferative activity on EGFR-mutant H1975 cells(IC50=0.83-3.31 μmolL-1) than gefitinib(IC50=8.59 μmolL-1). CONCLUSION: Compound 3b has the best inhibitory effect on H1975 cells. Therefore, 3b may be a potential anti-NSCLC agent for further investigation.

Design,synthesis and anti-NSCLC activity of hybrids of anilinopyrimidines and diazeniumdiolates / 中国药科大学学报

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.