Molecular elucidation of pancreatic elastase inhibition by baicalein

Abstract

The serine protease, elastase exists in various forms and plays diverse roles in the human body. Pharmacological inhibition of elastase has been investigated for its therapeutic role in managing conditions such as diabetes, pneumonia and arthritis. Sivelestat, a synthetic molecule, is the only elastase inhibitor to have been approved by any major drug regulatory authority (PMDA, in this case) – but still has failed to attain widespread clinical usage owing to its high price, cumbersome administration and obscure long-term safety profile. In order to find a relatively better-suited alternative, screening was conducted using plant flavonoids, which yielded baicalein, a molecule that showed robust inhibition against Pancreatic Elastase inhibition (IC₅₀: 3.53 μM). Other than having a considerably lower IC₅₀than sivelestat, baicalein is also cheaper, safer and easier to administer. While MicroScale Thermophoresis validated baicalein-elastase interaction, enzyme-kinetic studies, molecular docking and molecular dynamic simulation revealed the mode of inhibition to be non-competitive. Baicalein exhibited binding to a distinct allosteric site on the enzyme. The current study demonstrates the elastase inhibition properties of baicalein in an in-vitro and in-silico environment.

Communicated by Ramaswamy H. Sarma

Keywords:

• Baicalein
• elastase
• enzyme inhibition
• molecular interaction
• sivelestat

Acknowledgements

Authors are thankful to Savitribai Phule Pune University (SPPU), Pune for providing the facility and requirements needed for the study. RNG Thanks Rashtriya Uchchatar Shiksha Abhiyan (RUSA) funding. We are also thankful to Dr. Rohan Meshram, Bioinformatics Centre, SPPU, Pune for help in the MD simulation study.

Disclosure statement

No potential conflict of interest was reported by the authors.