Green synthesis, anti-proliferative evaluation, docking, and MD simulations studies of novel 2-piperazinyl quinoxaline derivatives using hercynite sulfaguanidine-SA as a highly efficient and reusable nanocatalyst

In this study, the immobilization of sulfaguanidine-SA on the surface of FeAl(2)O(4) (hercynite) MNPs (magnetic nanoparticles) as a novel acid nanocatalyst has been successfully reported for the synthesis of 2-(piperazin-1-yl) quinoxaline derivatives via a one-pot multiple-component reaction under green conditions. The products were characterized by SEM, TEM, TGA, EDS, BET technique, VSM, and FTIR. This series of novel 2-piperazinyl quinoxaline derivatives containing isatin-based thio/semicarbazones and/or Schiff bases of Metformin were evaluated for anticancer activity against both human ovarian and colon-derived tumor cell lines by MTT colorimetric assay. Although most of the investigated hybrid compounds exhibited excellent anti-proliferative activities and high selectivity index (SI) values, the promising compounds N′-[4-(quinoxaline-2-yl)-piperazine-1-yl]methyl-5-chloro-1-H-indole,2,3-dion-3-metformin 4c and N′-[4-(quinoxaline-2-yl)-piperazine-1-yl]methyl-5-bromo-1-H-indole,2,3-dion-3-metformin 4b proved to be the most potent anti-proliferative agents (IC50 values < 1 μM). Molecular docking and dynamics simulation suggest that these hybrid compounds can be wrapped in the catalytic cavity of c-Kit tyrosine kinase receptor and the binding pocket of P-glycoprotein with high scores. Thus, 2-piperazinyl quinoxaline linked isatin-based N-Mannich bases of metformin and/or thio/semicarbazones might be served as suitable candidates for further investigations to develop a new generation of multi-target cancer chemotherapy agents.