Synthesis, in vitro antitumor activity and molecular modeling studies of a new series of benzothiazole Schiff bases

A new series of benzothiazole Schiff bases 3–29 was synthesized and screened for antitumor activity against cervical cancer (Hela) and kidney fibroblast cancer (COS-7) cell lines. Results indicated that compounds 3, 14, 19, 27 and 28 have promising activity against Hela cell line with IC50 values of 2.41, 3.06, 6.46, 2.22 and 6.25 μmol/L, respectively, in comparison to doxorubicin as a reference antitumor agent (IC50 2.05 μmol/L). In addition, compound 3 displayed excellent activity against COS-7 cell line with IC50 value of 4.31 μmol/L in comparison to doxorubicin (IC50 3.04 μmol/L). In the present work, structure based pharmacophore mapping, molecular docking, protein-ligand interaction, fingerprints and binding energy calculations were employed in a virtual screening strategy to identify the interaction between the compounds and the active site of the putative target, EGFR tyrosine kinase. Molecular properties, toxicity, drug-likeness, and drug score profiles of compounds 3, 14, 19, 27, 28 and 29 were also assessed.

Graphical abstractCompound 3 with IC50 values of 2.41 and 4.31 μmol/L against Hela and COS-7 cell lines, respectively, was proved to be the most active member in this study.Figure optionsDownload full-size imageDownload as PowerPoint slide