Synthesis, in silico, and in vivo 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 6a-g, 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 6 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 6 b could be a potent anti-inflammatory compound, while in silico studies suggest its interaction with some critical enzymes in the inflammatory response.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

Keywords:

• Pregnane
• anti-inflammatory
• molecular docking
• molecular dynamics
• TPA model

Acknowledgements

The authors are thankful to Eduardo Tena-Betancourt, Facultad Mexicana de Medicina, Universidad La Salle-México for providing experimental animals, and technical assistance within in vivo experiments. The authors are thankful to Universidad La Salle-México for additional funding through project NEC-07/18.

Disclosure statement

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were following the ethical standards of Universidad La Salle México, described in protocol FMM/SICUAL/009/2018 in concordance with NOM-062-ZOO-1999.

Data availability statement

Original spectral data of each compound can be obtained from E.S-C.