Design, synthesis, and biological evaluation of novel benzo[b]thiophene-diaryl urea derivatives as potential anticancer agents

Abstract

A hybrid pharmacophore approach was applied to design and synthesize a series of benzo[b]thiophene-diaryl urea derivatives 17a–g with potential anticancer effect. In vitro antiproliferative activities of all target compounds were evaluated against HT-29 and A549 cancer cell lines. Three compounds 17b, 17d, and 17f exhibited antiproliferative activities on both cell lines comparable to that of the positive reference drug sorafenib. Notably, compound 17d demonstrated the highest activity with IC50 values of 5.91 and 14.64 μM on HT-29 and A549 cells, respectively. It also induced apoptosis and cell cycle arrest at the G0/G1 phase on HT-29 cells based on DAPI staining and propidium iodide (PI) staining followed by flow cytometry analyses. Molecular docking studies revealed that 17d can bind well to the active site of VEGFR2 receptor. Collectively, compound 17d can be considered as a promising scaffold amenable for further optimization towards the development of new anticancer agents.