Design, Synthesis, and Antitumor Activity of Erlotinib Derivatives

Nineteen erlotinib derivatives bearing different 1,2,3-triazole moieties were designed, synthesized, and evaluated for their potential against different cancer cell lines. The structures of the synthesized compounds were confirmed via H-1 NMR, C-13 NMR, and HR MS. Preliminary antitumor activity assay results suggested that some compounds showed remarkable inhibitory activity against different cancer cell lines including the corresponding drug-resistant ones. Among these compounds, 3d was the most promising one with an IC50 of 7.17 +/- 0.73 mu M (KYSE70TR), 7.91 +/- 0.61 mu M (KYSE410TR), 10.02 +/- 0.75 mu M (KYSE450TR), 5.76 +/- 0.3 3 mu M (H1650TR), and 2.38 +/- 0.17 mu M (HCC827GR). A preliminary mechanism study suggested that compound 3d suppressed cancer cell proliferation through the EGFR-TK pathway.