| 000 | 03177nlm1a2200409 4500 | ||
|---|---|---|---|
| 001 | 651577 | ||
| 005 | 20231030041040.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\16826 | ||
| 035 | _aRU\TPU\network\16729 | ||
| 090 | _a651577 | ||
| 100 | _a20161116a2016 k y0engy50 ba | ||
| 101 | 0 |
_aeng _deng |
|
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aCinnoline derivatives as human neutrophil elastase inhibitors _fM. P. Giovannoni, I. A. Schepetkin, L. Crocetti [et al.] |
|
| 203 |
_aText _celectronic |
||
| 300 | _aTitle screen | ||
| 330 | _aCompounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50value = 56 nM) and chemical stability (t1/2 = 114 min). Analysis of reaction kinetics revealed that these cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydroxyl group at the amido moiety, and cinnoline derivatives containing an ester function at C-4, which is the point of attack of Ser195. | ||
| 333 | _aРежим доступа: по договору с организацией-держателем ресурса | ||
| 461 | _tJournal of Enzyme Inhibition and Medicinal Chemistry | ||
| 463 |
_tVol. 31, iss. 4 _v[P. 628-639] _d2016 |
||
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aтруды учёных ТПУ | |
| 701 | 1 |
_aGiovannoni _bM. P. _gMaria Paola |
|
| 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 |
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| 701 | 1 |
_aCiciani _bG. _gGiovanna |
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| 701 | 1 |
_aCilibrizzi _bA. _gAgostino |
|
| 701 | 1 |
_aGuerrini _bG. _gGabriella |
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| 701 | 1 |
_aKhlebnikov _bA. I. _cChemist _cProfessor of Tomsk Polytechnic University _f1963- _gAndrey Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\33927 |
|
| 701 | 1 |
_aQuinn _bM. T. _gMark |
|
| 701 | 1 |
_aVergelli _bC. _gClaudia |
|
| 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 | _uhttp://dx.doi.org/10.3109/14756366.2015.1057718 | |
| 942 | _cCF | ||