Design, Synthesis, Biological Evaluation and Molecular Docking Studies of a New Series of Maleimide Derivatives

A series of novel maleimide derivatives were synthesized, with various heterocyclic compounds serving as side chains in the synthesis process. The structural characteristics of these compounds were elucidated through the application of ¹H-NMR spectroscopy, ¹³C-NMR (APT) spectroscopy, and high-resolution mass spectrometry (HRMS). The anti-cancer potential of these compounds was subsequently assessed in vitro, utilizing two distinct breast cancer cell lines, namely MDA-MB-231 and MCF-7, via MTT assay. Among the 12 newly synthesized compounds, 4 a, 4 b, 4 c, 4 d, 5 a, 5 b, 5 c and 5 d were determined to show the most promising anti-cancer activity against both breast cancer cell lines. Moreover, the morphological changes induced in the cells following a 24-hour incubation period with these compounds were observed using light microscopy. Additionally, molecular dynamics simulations were conducted to assess the stability of the bound conformations of the compounds to the target protein GSK-3β as obtained through molecular docking calculations.