Design, synthesis and anticancer activity of some novel thioureido-benzenesulfonamides incorporated biologically active moieties

BACKGROUND: Many thiourea derivatives have exhibited biological activities including anticancer activity through several mechanisms. On the other hand, benzenesulfonamide derivatives have proven to be good anticancer agents. Hybrids of both moieties could be further developed to explore their biological activity as anticancer. RESULTS: Novel series of thioureidobenzenesulfonamides incorporating miscellaneous biologically active moieties 3–17 were designed and synthesized utilizing 4-isothiocyanatobenzenesulfonamide 2 as strategic starting material. The structures of the newly synthesized compounds were established on the basis of elemental analyses, IR, (1)H-NMR, (13)C-NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against various cancer cell lines. Most of the synthesized compounds showed good activity, especially compounds 3, 6, 8, 9, 10, 15 and 16 which exhibited good activity higher than or comparable to the reference drugs, DCF and Doxorubicin, except breast cancer line. As a trial to suggest the mechanism of action of the active compounds, molecular docking on the active site of mitogen kinase enzyme (MK-2) was performed and good results were obtained especially for compound 3. CONCLUSION: Compounds 3, 6, 8, 9, 10, 15 and 16 may represent good candidates for further biological investigations as anticancer agents. Their cytotoxic activity could be due to their action as MK-2 enzyme inhibitors. [Figure: see text]