Synthesis and biological activity of nitric oxide-releasing derivatives of ferulic acid as potential agents for the treatment of chronic kidney diseases.

In order to search for novel potential agents for the treatment of chronic kidney diseases (CKD), nitric oxide (NO)-releasing derivatives (5a-c) of ferulic acid were synthesized and characterized by MS, 1H NMR, and elementary analysis. They showed different NO-releasing rate in the absence or presence of L-cysteine in vitro. In the adenine induced CKD rats, these compounds revealed reno-protective effect via lowering blood urea nitrogen (BUN), creatinine (Cr) in serum and malondialdehyde (MDA) in kidney, increasing NO and superoxide dismutase (SOD) level in kidney. Among them, 3-methoxy-4-(nitrooxy)ethoxy cinnamic acid (5a) was confirmed to have a higher NO-releasing rate in vitro and better effect in ameliorating adenine-induced kidney damage in rats.