Synthesis and analytical characterization of new thiazol-2-(3H)-ones as human neutrophil elastase (HNE) inhibitors

Letizia Crocetti, Gianluca Bartolucci, Agostino Cilibrizzi, Maria Paola Giovannoni, Gabriella Guerrini, Antonella Iacovone, Marta Menicatti, Igor A. Schepetkin, Andrei I. Khlebnikov, Mark T. Quinn, Claudia Vergelli

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9 Citations (Scopus)


Human neutrophil elastase (HNE) is a potent serine protease belonging to the chymotrypsin family and is involved in a variety of pathologies affecting the respiratory system. Thus, compounds able to inhibit HNE proteolytic activity could represent effective therapeutics. We present here the synthesis of new thiazol-2-(3H)-ones as an elaboration of potent HNE inhibitors with an isoxazol-5-(2H)-one scaffold that we recently identified. Two-dimensional NMR spectroscopic techniques and tandem mass spectrometry allowed us to correctly assign the structure of the final compounds arising from both tautomers of the thiazol-2-(3H)-one nucleus (N-3 of the thiazol-2-(3H)-one and 3-OH of the thiazole). All new compounds were tested as HNE inhibitors, and no activity was found at the highest concentration used (40 µM), demonstrating that the thiazol-2-(3H)-one is not a good scaffold for HNE inhibitors. Molecular modelling experiments indicate that the low-energy pose might limit the nucleophilic attack on the endocyclic carbonyl group of the thiazolone-based compounds by HNE catalytic Ser195, in contrast to isoxazol-5-(2H)-one analogues.

Original languageEnglish
Article number127
JournalChemistry Central Journal
Issue number1
Publication statusPublished - 2017


  • ERMS
  • Human neutrophil elastase
  • LC-MS/MS
  • Synthesis
  • Thiazol-2-(3H)-one

ASJC Scopus subject areas

  • Chemistry(all)

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