AUTHOR=Mao Long-fei , Wang Zhen-Zhen , Wu Qiong , Chen Xiaojie , Yang Jian-Xue , Wang Xin , Li Yue-Ming 

TITLE=Design, Synthesis, and Antitumor Activity of Erlotinib Derivatives

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.849364

DOI=10.3389/fphar.2022.849364

ISSN=1663-9812

ABSTRACT=<p>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 <italic>via</italic><sup>1</sup>H NMR, <sup>13</sup>C 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 IC<sub>50</sub> of 7.17 ± 0.73 μM (KYSE70TR), 7.91 ± 0.61 μM (KYSE410TR), 10.02 ± 0.75 μM (KYSE450TR), 5.76 ± 0.3 3 μM (H1650TR), and 2.38 ± 0.17 μM (HCC827GR). A preliminary mechanism study suggested that compound 3d suppressed cancer cell proliferation through the EGFR-TK pathway.</p>