| 000 | 03452nlm1a2200553 4500 | ||
|---|---|---|---|
| 001 | 656791 | ||
| 005 | 20231030041444.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\23271 | ||
| 090 | _a656791 | ||
| 100 | _a20171213a2017 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 102 | _aGB | ||
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aIsoxazol-5(2H)-one: a new scaffold for potent human neutrophil elastase (HNE) inhibitors _fC. Vergelli, I. A. Schepetkin, L. Crocetti [et al.] |
|
| 203 |
_aText _celectronic |
||
| 300 | _aTitle screen | ||
| 320 | _a[References: p. 830-831 (41 tit.)] | ||
| 330 | _aHuman neutrophil elastase (HNE) is an important target for the development of novel and selective inhibitors to treat inflammatory diseases, especially pulmonary pathologies. Here, we report the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with an isoxazol-5(2H)-one scaffold. The most potent compound (2o) had a good balance between HNE inhibitory activity (IC50value =20 nM) and chemical stability in aqueous buffer (t1/2=8.9 h). Analysis of reaction kinetics revealed that the most potent isoxazolone derivatives were reversible competitive inhibitors of HNE. Furthermore, since compounds 2o and 2s contain two carbonyl groups (2-N-CO and 5-CO) as possible points of attack for Ser195, the amino acid of the active site responsible for the nucleophilic attack, docking studies allowed us to clarify the different roles played by these groups. | ||
| 333 | _aРежим доступа: по договору с организацией-держателем ресурса | ||
| 461 | _tJournal of Enzyme Inhibition and Medicinal Chemistry | ||
| 463 |
_tVol. 32, iss. 1 _v[P. 821-831] _d2017 |
||
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _aIsoxazol-5(2H)-one | |
| 610 | 1 | _ahuman neutrophil elastase | |
| 610 | 1 | _aHNE inhibitor | |
| 610 | 1 | _achemical stability | |
| 610 | 1 | _amolecular docking | |
| 610 | 1 | _aизоксазолы | |
| 610 | 1 | _aнейтрофильная эластаза | |
| 610 | 1 | _aингибиторы | |
| 610 | 1 | _aхимическая стабильность | |
| 610 | 1 | _aмолекулярная стыковка | |
| 701 | 1 |
_aVergelli _bC. _gClaudia |
|
| 701 | 1 |
_aSchepetkin (Shchepyotkin) _bI. A. _cdoctor-biophysicist _cleading researcher of Tomsk Polytechnic University, candidate of medical science _f1962- _gIgor Aleksandrovich _2stltpush _3(RuTPU)RU\TPU\pers\37358 |
|
| 701 | 1 |
_aCrocetti _bL. _gLetizia |
|
| 701 | 1 |
_aIacovone _bA. _gAntonella |
|
| 701 | 1 |
_aGiovannoni _bM. P. _gMaria Paola |
|
| 701 | 1 |
_aGuerrini _bG. _gGabriella |
|
| 701 | 1 |
_aKhlebnikov _bA. I. _cChemist _cProfessor of Tomsk Polytechnic University _f1963- _gAndrey Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\33927 |
|
| 701 | 1 |
_aCiattini _bS. _gSamuele |
|
| 701 | 1 |
_aCiciani _bG. _gGiovanna |
|
| 701 | 1 |
_aQuinn _bM. T. _gMark |
|
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет (ТПУ) _bИнститут физики высоких технологий (ИФВТ) _bКафедра биотехнологии и органической химии (БИОХ) _h6810 _2stltpush _3(RuTPU)RU\TPU\col\18693 |
| 801 | 2 |
_aRU _b63413507 _c20201103 _gRCR |
|
| 856 | 4 | _uhttps://doi.org/10.1080/14756366.2017.1326915 | |
| 942 | _cCF | ||