| 000 | 04174nlm1a2200517 4500 | ||
|---|---|---|---|
| 001 | 668380 | ||
| 005 | 20231030042146.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\39605 | ||
| 035 | _aRU\TPU\network\35701 | ||
| 090 | _a668380 | ||
| 100 | _a20221110a2022 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 102 | _aCH | ||
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aDesign, synthesis and biological evaluation of novel O-substituted tryptanthrin oxime derivatives as c-Jun N-terminal kinase inhibitors _fI. A. Schepetkin (Shchepyotkin), A. R. Kovrizhina, K. S. Stankevich [et al.] |
|
| 203 |
_aText _celectronic |
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| 300 | _aTitle screen | ||
| 330 | _aThe c-Jun N-terminal kinase (JNK) family includes three proteins (JNK1-3) that regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival, and cell death. Therefore, JNK represents an attractive target for therapeutic intervention. Herein, a panel of novel tryptanthrin oxime analogs were synthesized and evaluated for JNK1-3 binding (Kd) and inhibition of cellular inflammatory responses (IC50). Several compounds exhibited submicromolar JNK binding affinity, with the most potent inhibitor being 6-(acetoxyimino)indolo[2,1-b] quinazolin-12(6H)-one (1j), which demonstrated high JNK1-3 binding affinity (Kd = 340, 490, and 180 nM for JNK1, JNK2, and JNK3, respectively) and inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcription activity in THP-1Blue cells and interleukin-6 (IL-6) production in MonoMac-6 monocytic cells (IC50 = 0.8 and 1.7 μM, respectively). Compound 1j also inhibited LPS-induced production of several other proinflammatory cytokines, including IL-1α, IL1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF) in MonoMac-6 cells. Likewise, 1j inhibited LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. Molecular modeling suggested modes of binding interaction of selected compounds in the JNK3 catalytic site that were in agreement with the experimental JNK3 binding data. Our results demonstrate the potential for developing antiinflammatory drugs based on these nitrogen-containing heterocyclic systems | ||
| 461 | _tFrontiers in Pharmacology | ||
| 463 |
_tVol. 13 _v[958687, 14 p.] _d2022 |
||
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _aanti-inflammatory | |
| 610 | 1 | _a11H-indeno[1,2-b]quinoxalin-11-one | |
| 610 | 1 | _ainterleukin-6 | |
| 610 | 1 | _ac-Jun N-terminal kinase | |
| 610 | 1 | _anuclear factor-κB | |
| 610 | 1 | _aoxime | |
| 610 | 1 | _atryptanthrin | |
| 610 | 1 | _aпротивовоспалительные средства | |
| 610 | 1 | _aинтерлейкины | |
| 610 | 1 | _aоксимы | |
| 610 | 1 | _aтриптофаны | |
| 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 |
_aKovrizhina _bA. R. _cbiotechnology specialist _cResearch Engineer of Tomsk Polytechnic University _f1995- _gAnastasia Ruslanovna _2stltpush _3(RuTPU)RU\TPU\pers\46608 |
|
| 701 | 1 |
_aStankevich _bK. S. _cPhysicist _cEngineer Tomsk Polytechnic University _f1992- _gKsenia Sergeevna _2stltpush _3(RuTPU)RU\TPU\pers\37546 |
|
| 701 | 1 |
_aKhlebnikov _bA. I. _cChemist _cProfessor of Tomsk Polytechnic University _f1963- _gAndrey Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\33927 |
|
| 701 | 1 |
_aKirpotina _bL. N. _gLiliya |
|
| 701 | 1 |
_aQuinn _bM. T. _gMark |
|
| 701 | 1 |
_aCook _bM. J. _gMatthew |
|
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет _bИнженерная школа природных ресурсов _bОтделение химической инженерии _h8085 _2stltpush _3(RuTPU)RU\TPU\col\23513 |
| 801 | 2 |
_aRU _b63413507 _c20230111 _gRCR |
|
| 856 | 4 | _uhttps://doi.org/10.3389/fphar.2022.958687 | |
| 942 | _cCF | ||