On the basis of the strategy of “multifunctional drugs”, a series of novel matrix metalloproteinase inhibitors (MMPIs) containing benzofuroxan scaffold as a nitric oxide donor were designed, synthesized and evaluated. All synthesized compounds, especially 16a, exhibited potent MMP-2,9 inhibitory activities, anti-proliferative activities and could produce high levels of NO in Hela cells. They were also evaluated for both of their anti-invasion and anti-angiogenesis effects. Furthermore, compared with LY52, 16a demonstrated competitive antitumor activity in vivo. These hybrid NO-MMPIs might offer suitable scaffolds to develop valuable MMP inhibitors for the further discovery of novel anti-cancer drugs.

在“多功能药物”策略的基础上，设计，合成和评估了一系列新型的以苯并呋喃聚糖骨架为一氧化氮供体的基质金属蛋白酶抑制剂（MMPI）。所有合成的化合物，尤其是16a，均显示出有效的MMP-2,9抑制活性，抗增殖活性，并可能在Hela细胞中产生高水平的NO。还评估了它们的抗侵袭和抗血管生成作用。此外，与LY52相比，16a在体内表现出竞争性抗肿瘤活性。这些杂合的NO-MMPI可能会提供合适的支架，以开发有价值的MMP抑制剂，以进一步发现新型抗癌药物。