JOURNAL OF HETEROCYCLIC CHEMISTRY, vol.59, no.3, pp.518-532, 2022 (SCI-Expanded)
EGFR (epidermal growth factor receptor) tyrosine kinases are frequently used in recent years, especially in small cell lung cancer. As with all other anticancer drugs, problems such as high side-effect profiles and resistance to anticancer drugs call for new antiproliferative compounds. In the light of the above information, novel quinoxalin-oxadiazole derivatives were synthesized as EGFR inhibitors in this study. Synthesis of compounds (3a-3j) was performed according to the literature methods. Their structures were elucidated by H-1-NMR, C-13-NMR, and HRMS spectroscopic methods. Structure elucidation was performed for compound 3e using 2D NMR technique. MTT test was performed to assess the cell proliferation effects of the different compounds on lung and mammary cell lines (A549, MCF7). In addition, obtained compounds (3a-3j) were screened against healthy CCD19-Lu cell line (human lung fibroblast normal cells) to determine selectivity of the cytotoxic activities. Among the tested compounds, 3e and 3j showed significant cytotoxic activity against A549 cancer cell. Moreover, compound 3g and 3h displayed good activity. And the compounds 3e and 3j performed significant EGFR inhibition. Interaction modes of the compounds 3e, 3j were investigated against EGFR tyrosine kinase by means of docking studies. As a result of the studies, the importance of the quinoxaline ring and the NO2 substituent has been understood. In future studies, it is planned to make modifications by keeping these two structures constant. The activity can be contributed by using other heterocyclic rings instead of the oxadizaole ring.