Cytotoxicity, tyrosine kinase inhibition of novel pyran, pyridine, thiophene, and imidazole derivatives

Abstract

In this work, we are interested to use multicomponent reactions of cyclohexan‐1,3‐dione with different reagents for synthesizing new derivatives of pyran, pyridine, thiophene, and imidazole with antitumor activities. Twenty‐two newly synthesized derivatives were selected and tested for their anticancer potency. Several of these compounds exhibited quite interesting potencies toward three human tumor cell lines, namely NCI‐H460 (non‐small cell lung cancer), SF‐268 (CNS cancer), and MCF‐7 (breast adenocarcinoma), especially when compared to that of reference drugs, doxorubicin and 5‐Fu.Compounds 5b, 5c, 7b, 9b, 14a, 16c, 18a, 19c, 20b, and 22b, were found to be the most cytotoxic compounds toward the selected cell lines. On the other hand, 7b, 14a, 16c, 19c, and 22b revealed high inhibitions toward the tyrosine kinases. Active compounds against VEGFR‐2, 14a, 16c, and 19c, were docked inside VEGFR‐2enzyme to show the interaction between the tested compounds and the amino acids of the active site.