Phenylsulfonylfuroxan NO-donor phenols: Synthesis and multifunctional activities evaluation

Abstract

Phenylsulfonyfuroxan nitric oxide (NO)-donor phenols were designed, synthesized and evaluated. The compounds were designed through a symbiotic approach using selected phenols and phenylsulfonylfuroxan NO-donor. The antioxidant activities of the hybrid compounds T₂-T₆ showed to be good in vivo. Compounds T₄ and T₆ revealed excellent yeast α-glucosidase inhibitory activity and anti-glycosylation activity. All of the compounds exhibited strong NO releasing activity and significant anti-platelet aggregation activity. The inhibition of platelet aggregation was more than 50% at low concentration (1.5μM) and 95% at higher concentration (15μM and 150μM). The vasodilatation experiment demonstrated that the six compounds under test exhibited definite vasodilation activity (pIC₅₀ ranged from 5.698 to 6.383), especially compound T₆ (pIC₅₀ was 6.383) which was similar to sodium nitroprusside (pIC₅₀ was 6.786). Both anticoagulant and vasodilatation effects were correlated with their NO releasing activities. These hybrid phenylsulfonyfuroxan-based NO-donor phenols offer a multifunctional prodrug design concept for the development of therapeutic or preventive agents for metabolic syndrome.

Keywords: Anti-glycosylation; Anti-platelet aggregation; Antioxidant; Metabolic syndrome; Phenylsulfonyfuroxan; Vasodilatation; Yeast α-glucosidase.