Synthesis, <i>in silico</i>, and <i>in vivo</i> anti-inflammatory evaluation of 3β-cinnamoyloxy substituted pregna-4,16-diene-6,20-diones derivatives

Abstract

Pregnane derivatives have been studied mainly for their 5α-reductase activity. However, the anti-inflammatory activities of such compounds are still poorly explored. In the search for new anti-inflammatory agents, seven new pregnane derivatives <b>6a</b>-<b>g</b>, with cinnamic acid esters at C-3 were prepared and fully characterized. The anti-inflammatory activity of compounds was assessed in TPA induced mice ear model. From them, compound <b>6 b</b> was the most active to reduce edema, with an ED₅₀ of 0.017 mg/ear. Also, Molecular Docking and Molecular Dynamics studies were performed to identify a potential molecular target related to the inflammatory process. The in vivo results suggest that <b>6 b</b> could be a potent anti-inflammatory compound, while in silico studies suggest its interaction with some critical enzymes in the inflammatory response.