Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Diosgenin Meta-Derivatives as Anti-Inflammatory Agents

Abstract

AbractDiosgenin (DG) is a natural steroidal compound with a variety of biological activities. Studies have shown that the anti-inflammatory activity of DG is particularly prominent, which is highly effective with low side effects and can achieve therapeutic effects not achieved by many non-steroidal anti-inflammatory drugs. We used DG as raw material to synthesize a series of novel DG F-spiroacetal opened derivatives, and conducted preliminary in vitro anti-inflammatory activity. In this paper, we designed and synthesized three kinds of novel diosgenin derivatives, and screened the derivatives for IL-6 and NO release inhibitory activity. The results showed that 4m (1.710 μM) was the more significant derivative in reducing NO levels (IC 50 of 0.449 ± 0.050 μM), and the molecular docking results indicated that 4m had a good affinity for p65 protein. We believe that the study of DG derivatives could enrich the conformational relationship of DG and provide scientific basis for the in-depth study of anti-inflammatory activity of DG and its derivatives.

Keywords: Diosgenin derivatives, Synthesis, Anti-inflammatory agent, Molecular docking studies