An overview of phenylsulfonylfuroxan-based nitric oxide donors for cancer treatment.

Nitric oxide (NO) is a gaseous molecule integral to numerous physiological processes, including tumor modulation, cardiovascular regulation, and systemic physiological functions. Its dual role in promoting and inhibiting tumor growth makes it a focal point of contemporary oncological research. Phenylsulfonylfuroxan, a classical NO donor, has been shown to significantly elevate NO levels, thereby inducing apoptosis and inhibiting proliferation and metastasis in tumor cells. It enhances the efficacy of chemotherapy, radiotherapy, and immunotherapy, reverses multidrug resistance (MDR), and impedes tumor progression. Notably, phenylsulfonylfuroxan have the ability to trigger ferroptosis in cancer cells by binding covalently to inhibit glutathione peroxidase 4 (GPX4). Recent developments in phenylsulfonylfuroxan-based therapies have positioned them as crucial in the advancement of cancer treatment modalities. This review elucidates the mechanism by which phenylsulfonylfuroxan releases NO and summarizes the significant advancements over the past 16 years in the research and development of phenylsulfonylfuroxan conjugates with various anticancer agents for targeted cancer therapy.