Synthesis and hypoglycemic activities of nitric oxide-donating salsalate derivatives

Aim:To study the synthesis and hypoglycemic activities of nitric oxide-donating salsalate derivatives and search for novel anti-diabetic agents.Methods:Using salsalate as a lead compound,nitrates were incorporated to 2′-carboxyphenyl of salsalate via a variety of linkers,giving target compounds 2a-2e,4a,4b,6a and 6b.And the compounds′ activities of increasing the glucose consumption in liver tumor cells were evaluated by GOD-POD assay.In addition,NO-release of the compounds was determined by Griess assay.Results:The structures of all the target compounds were confirmed by IR,MS and 1H NMR.The screening results demonstrated that all tested compounds exhibited hypoglycemic activities to various extents,especially compound 2a,2b,4b showing more potent activity than salsalate did.Conclusion:The hypoglycemic activities of NO-donating salsalate derivatives are probably by NO-release mechanism.Compound 2a is promising for further investigation.