Study on New Lead Compounds of Neutrophil Elastase Inhibitor

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD) is clinical syndrome of respiratory failure with high morbidity and mortality in the worldwide. Although the pathophysiology of ALI has been made in understanding, however, there is still lack innovative and useful medicine in clinical to reduce mortality. Emerging data suggest that excessive release of human neutrophil elastase (HNE) mediates tissue damage, and therefore prolonged neutrophil accumulation has an important role in the pathogenesis of many diseases. Sivelestat is the only nonpeptidic inhibitor marketed. However, the use of sivelestat was limited by its poor pharmacokinetics and serious risks of organ toxicity because it irreversibly inhibits HNE. Thus, HNE inhibitor may prove to be targets for the generation of agents in the treatment of neutrophilic inflammatory disease. A previous study enabled us to identify two components (WWH-31 and sirtinol) and two aqueous extracts of Smitax glabra and Kochia scoparia, which selectively inhibited HNE activity. Of these, WWH-31 showed potent activities in in vivo and in vitro studies. In addition, WWH-31 obtained US and Taiwan patents. Therefore, the studies on pharmacokinetics and toxicity of WWH-31 will carry out. Secondary, sirtinol derivatives will be designed, synthesized, evaluated, and developed using structural-based design. Furthermore, the pharmacokinetic analysis of bioactive derivatives will also be determined herein. Finally, the bioactive components of Smilax glabra and Kochia scoparia will be confirmed using the bioactive-guide fractionation.

Project IDs

Project ID:PC10507-1266
External Project ID:MOST105-2320-B182-009
Effective start/end date01/08/1631/07/17


  • human neutrophil elastase inhibitor
  • sirtinol
  • Acute lung injury
  • Smilax glabra
  • Kochia scoparia


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