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dc.contributor.authorCrocetti, Letizia
dc.contributor.authorBartolucci, Gianluca
dc.contributor.authorCilibrizzi, Agostino
dc.contributor.authorGiovannoni, Maria Paola
dc.contributor.authorGuerrini, Gabriella
dc.contributor.authorIacovone, Antonella
dc.contributor.authorMenicatti, Marta
dc.contributor.authorSchepetkin, Igor A.
dc.contributor.authorKhlebnikov, Andrei I.
dc.contributor.authorQuinn, Mark T.
dc.contributor.authorVergelli, Claudia
dc.date.accessioned2018-07-20T17:33:09Z
dc.date.available2018-07-20T17:33:09Z
dc.date.issued2018-01
dc.identifier.citationCrocetti, Letizia, Gianluca Bartolucci, Agostino Cilibrizzi, Maria Paola Giovannoni, Gabriella Guerrini, Antonella Iacovone, Marta Menicatti, Igor A Schepetkin, Andrei I Khlebnikov, Mark T Quinn, and Claudia Vergelli. "Synthesis and analytical characterization of new thiazol-2-(3H)-ones as human neutrophil elastase (HNE) inhibitors." Chemistry Central Journal 11, no. 1 (January 2018): 1-15. DOI: 10.1186/s13065-017-0358-1.en_US
dc.identifier.issn1752-153X
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/14657
dc.description.abstractHuman 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.en_US
dc.description.sponsorshipNational Institutes of Health IDeA Program COBRE Grant GM110732; USDA National Institute of Food and Agriculture Hatch Project 1009546; the Montana State University Agricultural Experiment Stationen_US
dc.language.isoenen_US
dc.rightsCC BY 4.0, This license lets others distribute, remix, tweak, and build upon your work, even commercially, as long as they credit you for the original creation. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleSynthesis and analytical characterization of new thiazol-2-(3H)-ones as human neutrophil elastase (HNE) inhibitorsen_US
dc.typeArticleen_US
mus.citation.extentfirstpage1en_US
mus.citation.extentlastpage15en_US
mus.citation.issue1en_US
mus.citation.journaltitleChemistry Central Journalen_US
mus.citation.volume11en_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1186/s13065-017-0358-1en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.data.thumbpage5en_US
mus.contributor.orcidQuinn, Mark T.|0000-0001-8114-5073en_US


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CC BY 4.0, This license lets others distribute, remix, tweak, and build upon your work, even commercially, as long as they credit you for the original creation. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.
Except where otherwise noted, this item's license is described as CC BY 4.0, This license lets others distribute, remix, tweak, and build upon your work, even commercially, as long as they credit you for the original creation. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.

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