| 000 | 04976n m1a2200577 4500 | ||
|---|---|---|---|
| 001 | 668679 | ||
| 005 | 20231030042156.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\39916 | ||
| 035 | _aRU\TPU\network\37574 | ||
| 090 | _a668679 | ||
| 100 | _a20230117a2022 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 102 | _aCH | ||
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aNeuroprotective Effects of the Lithium Salt of a Novel JNK Inhibitor in an Animal Model of Cerebral Ischemia-Reperfusion _fI. A. Schepetkin (Shchepyotkin), G. A. Shernysheva, O. I. Aliev [et al.] |
|
| 203 |
_aText _celectronic |
||
| 300 | _aTitle screen | ||
| 320 | _a[References: 77 tit.] | ||
| 330 | _aThe c-Jun N-terminal kinases (JNKs) regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival, and cell death. Therefore, JNKs represent attractive targets for therapeutic intervention. In an effort to develop improved JNK inhibitors, we synthesized the lithium salt of 11H-indeno[1,2-b]quinoxaline-11-one oxime (IQ-1L) and evaluated its affinity for JNK and biological activity in vitro and in vivo. According to density functional theory (DFT) modeling, the Li+ ion stabilizes the six-membered ring with the 11H-indeno[1,2-b]quinoxaline-11-one (IQ-1) oximate better than Na+. Molecular docking showed that the Z isomer of the IQ-1 oximate should bind JNK1 and JNK3 better than (E)-IQ-1. Indeed, experimental analysis showed that IQ-1L exhibited higher JNK1-3 binding affinity in comparison with IQ-1S. IQ-1L also was a more effective inhibitor of lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in THP-1Blue monocytes and was a potent inhibitor of proinflammatory cytokine production by MonoMac-6 monocytic cells. In addition, IQ-1L inhibited LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. In a rat model of focal cerebral ischemia (FCI), intraperitoneal injections of 12 mg/kg IQ-1L led to significant neuroprotective effects, decreasing total neurological deficit scores by 28, 29, and 32% at 4, 24, and 48 h after FCI, respectively, and reducing infarct size by 52% at 48 h after FCI. The therapeutic efficacy of 12 mg/kg IQ-1L was comparable to that observed with 25 mg/kg of IQ-1S, indicating that complexation with Li+ improved efficacy of this compound. We conclude that IQ-1L is more effective than IQ-1S in treating cerebral ischemia injury and thus represents a promising anti-inflammatory compound. | ||
| 461 | _tBiomedicines | ||
| 463 |
_tVol. 10, iss. 9 _v[2119, 16 p.] _d2022 |
||
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _ac-Jun N-terminal kinase | |
| 610 | 1 | _a11H-indeno[1,2-b]quinoxalin-11-one | |
| 610 | 1 | _aoxime | |
| 610 | 1 | _ainterleukin-6 | |
| 610 | 1 | _anuclear factor-κB | |
| 610 | 1 | _alithium salt | |
| 610 | 1 | _astroke | |
| 610 | 1 | _aоксимы | |
| 610 | 1 | _aинтерлейкины | |
| 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 |
_aShernysheva _bG. A. _gGalina Anatoljevna |
|
| 701 | 1 |
_aAliev _bO. I. _gOleg Ibragimovich |
|
| 701 | 1 |
_aKirpotina _bL. N. _gLiliya Nikolaevna |
|
| 701 | 1 |
_aSmol’iakova _bV. I. _gVera Ivanovna |
|
| 701 | 1 |
_aOsipenko _bA. N. _gAnton Nikolaevich |
|
| 701 | 1 |
_aPlotnikov _bM. B. _gMark Borisovich |
|
| 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 |
_aKhlebnikov _bA. I. _cChemist _cProfessor of Tomsk Polytechnic University _f1963- _gAndrey Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\33927 |
|
| 701 | 1 |
_aPlotnikov _bE. V. _cchemist _cAssociate Professor of Tomsk Polytechnic University, Candidate of Chemical Sciences _f1983- _gEvgeny Vladimirovich _2stltpush _3(RuTPU)RU\TPU\pers\32469 |
|
| 701 | 1 |
_aQuinn _bM. T. _gMark |
|
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет _bИсследовательская школа химических и биомедицинских технологий _c(2017- ) _h8120 _2stltpush _3(RuTPU)RU\TPU\col\23537 |
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет _bИнженерная школа новых производственных технологий _bНаучно-образовательный центр Н. М. Кижнера _h7872 _2stltpush _3(RuTPU)RU\TPU\col\23556 |
| 801 | 2 |
_aRU _b63413507 _c20230331 _gRCR |
|
| 856 | 4 | _uhttp://earchive.tpu.ru/handle/11683/74930 | |
| 856 | 4 | _uhttps://doi.org/10.3390/biomedicines10092119 | |
| 942 | _cCF | ||