Design, synthesis and molecular docking of novel N,N-dimethylbenzenesulfonamide derivatives as potential antiproliferative agents

Abstract

Novel pyridine, thiophene, thiazole, chromene and benzochromene derivatives bearing a N,N-dimethylbenzenesulfonamide moiety 6–20 were synthesized. The target compounds were obtained through employing a series of heterocyclization reactions utilizing the key intermediate hydrazide hydrazone derivative 3. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, ¹H-NMR and ¹³C-NMR spectral data. All the newly synthesized compounds were evaluated for their in vitro antiproliferative activity against the human breast cancer cell line MCF-7. Biological screening results showed that sulfonamides 6, 9, 11, 16 and 17 with IC₅₀ values 21.81, 25.50, 20.60, 25.83 and 31.20 μM, respectively, possessed higher antiproliferative activity compared to doxorubicin, IC₅₀ value 32.00 μM, as position control. Molecular docking study was also performed to assess the binding mode of the synthesized sulfonamides with their potential biomolecular target, carbonic anhydrase IX (CA IX), which is usually highly expressed in some types of cancer cells.

• Antiproliferative activity
• CA IX
• chromene
• pyridine
• sulfonamide
• thiazole
• thiophene

Acknowledgements

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University.