Design, cytotoxic effects on breast cancer cell line (MDA-MB 231), and molecular docking of some maleimide-benzenesulfonamide derivatives

A group of novel maleimide-benzenesulfonamide derivatives 3a-d was designed and synthesized for their evaluation as a potential anti-breast cancer agent. The structures of these derivatives were confirmed by their 1H, 13C NMR, Mass, FT-IR spectral data, and melting points. The cytotoxic activity (in vitro) of the selected molecules against MDA-MB231 ​cell line was evaluated by MTT method. Among them, compounds 3a and 3d exhibited a significant cytotoxicity with the IC50 value of 1.61 and 1.26 ​μM, respectively, whereas compounds 3b and 3c showed a moderate cytotoxicity with IC50 values of 0.45 and 1.12 ​μM, respectively against MDA-MB231 ​cells. Docking modeling of the synthesized compounds 3a-d into binding sites of human aromatase protein (PDB ID: 4GL7) was performed to investigate if these derivatives possess analogous binding mode to breast cancer proteins. Docking results showed these compounds have efficient interactions such as hydrogen bonding, Van der Waals interactions, and hydrophobic interactions with the active site residues of the aromatase protein (PDB ID: 4GL7). The low binding energies and a number of hydrogen bonding indicated that the maleimide-benzenesulfonamide derivatives might be considered as a promising anti-breast cancer agent with further developments in drug discovery. [Display omitted] •Metastases mostly disseminate late from primary breast tumors, keeping most drivers.•Design and synthesis of novel like drugs with potential anti-breast cancer.•The combination of pharmaceutical molecules is important for identifying target various diseases.•Molecular docking data help to understand the ligand-enzymes interactions.