The stilbene and dibenzo[b,f]oxepine derivatives as anticancer compounds

Damian Garbicz , Piotr Tobiasz , Filip Borys , Tomasz Pilżys , Michał Marcinkowski , Marcin Poterała , Elżbieta Grzesiuk , Hanna Krawczyk

Abstract

In the present study, the synthesis and cytotoxic effect of six stilbenes and three oxepine derivatives against two cancerous – HeLa and U87, and two normal – EUFA30 and HEK293 cell lines has been reported. The results of cytotoxic assay and flow cytometry analysis revealed that compounds 9-nitrobenzo[b]naphtho[1,2-f]oxepine (4), (E)-3,3′,4,4′,5,5′-hexamethoxystilbene (6) and 4-hydroxy-2′,4′-dinitrostilbene (8) were the most active and their interaction with tubulin (crystal structure from PDB) has been analyzed by computer molecular modeling. Molecular docking of these compounds on colchicine binding site of the tubulin indicates the interaction of (4), (6) and (8) with tubulin. The compound (4) could interact stronger with tubulin, relative to colchicine, however, with no selectivity of action against cancer and normal cells. Conversely, compounds (6) and (8) interact more weakly with tubulin, relative to colchicine but they act more selectively towards cancerous versus normal cell lines. Obtained results proved that the compounds that are the most active against cancerous cells operate through tubulin binding.