Design, synthesis and biological evaluation of novel hybrids of quinazoline derivatives and phenylsulfonylfuroxan as potential anti-tumor agents

In this study, a series of novel quinazoline/phenylsulfonylfuroxan hybrids were designed, synthesized, and biologically evaluated against five human cancer cell lines (H1975, MCF-7, Eca-109, MGC-803 and A549). The most of hybrids displayed considerable antiproliferative activities against the tested five cancer cells, while compound 25q exhibited the most potent antiproliferative activity with the IC50 values of 1.67 and 1.88 mu M against H1975 cells and MGC-803 cells, respectively. Further in vitro mechanistic studies showed that 25q had the remarkable capacity to suppress the migration of H1975 cells. Besides, 25q also arrested the H1975 cell cycle in the G0/G1 phase and mediated cell apoptosis. NO releasing assay confirmed that the designed hybrids could generate a significant amount of NO and the consistent tendency between NO releasing abilities and antiproliferative activities. Among these compounds, 25q also exhibited the most potent NO releasing ability. Overall, all these studies indicate that the designed quinazoline/phenylsulfonylfuroxan hybrids have significant anti-tumor activities and excellent NO releasing ability and 25q has the potential to act as a valuable lead compound for the development of anti-tumor agents.