Antiproliferative activity, wound healing, and theoretical computational studies of compounds including the benzimidazole moiety.

In this study, compounds, including the benzimidazole moiety, were prepared and characterized by spectroscopic methods. These distinct heterocyclic compounds (3a-d) were tested to investigate changes in cell viability at different incubation periods using the MTT assay in lung and colon cancer cell lines, which are widely distributed worldwide. Among the synthesized compounds, 3d, in particular, demonstrated significant cytotoxicity against DLD-1 and A549 cancer cell lines, showing strong potential as a lead compound. In here, wound healing tests of benzimidazole derivatives were also conducted in vitro on HEK-293T cells. It was found that compounds 3a-c increased wound healing in normal HEK-293T cells, whereas compound 3d, which was found to have the highest cytotoxic activities in DLD-1 for 72 h and 96 h with IC values of 26.65 ± 3.62 and 22.21 ± 1.61 μM, respectively, and in A549 for 72 h with IC value of 19.75 ± 2.49 μM, was ineffective in wound healing. The in silico ADME properties for compound 3d, which exhibited high cytotoxicity in cancer cells, were investigated using the SwissADME online server. Furthermore, toxicity properties were investigated using the Protox-II online server. The binding potential of the compounds to histone deacetylase was evaluated using molecular docking methods, and a new compound 3d was found to exhibit the highest binding potential to the target. The compound interacted to the enzyme with less strength than the standard inhibitor, vorinostat. The stability of the HDAC6-3d complex was evaluated through molecular dynamics (MD) simulation. The MD simulation result showed that the HDAC6-3d complex could be stable during the 200 ns simulation period.