| 000 | 04758nlm1a2200505 4500 | ||
|---|---|---|---|
| 001 | 664967 | ||
| 005 | 20231030041947.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\36152 | ||
| 035 | _aRU\TPU\network\35617 | ||
| 090 | _a664967 | ||
| 100 | _a20210604a2021 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 102 | _aCH | ||
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aSynthesis, Biological Evaluation, and Molecular Modeling of Aza-Crown Ethers _fS. S. Basok, I. A. Schepetkin (Shchepyotkin), A. I. Khlebnikov [et al.] |
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| 203 |
_aText _celectronic |
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| 300 | _aTitle screen | ||
| 320 | _a[References: 60 tit.] | ||
| 330 | _aSynthetic and natural ionophores have been developed to catalyze ion transport and have been shown to exhibit a variety of biological effects. We synthesized 24 aza- and diaza-crown ethers containing adamantyl, adamantylalkyl, aminomethylbenzoyl, and e-aminocaproyl substituents and analyzed their biological effects in vitro. Ten of the compounds (8, 10–17, and 21) increased intracellular calcium ([Ca2+]i) in human neutrophils, with the most potent being compound 15 (N,N’-bis[2-(1-adamantyl)acetyl]-4,10-diaza-15-crown-5), suggesting that these compounds could alter normal neutrophil [Ca2+]i flux. Indeed, a number of these compounds (i.e., 8, 10–17, and 21) inhibited [Ca2+]i flux in human neutrophils activated by N-formyl peptide (fMLF). Some of these compounds also inhibited chemotactic peptide-induced [Ca2+]i flux in HL60 cells transfected with N-formyl peptide receptor 1 or 2 (FPR1 or FPR2). In addition, several of the active compounds inhibited neutrophil reactive oxygen species production induced by phorbol 12-myristate 13-acetate (PMA) and neutrophil chemotaxis toward fMLF, as both of these processes are highly dependent on regulated [Ca2+]i flux. Quantum chemical calculations were performed on five structure-related diaza-crown ethers and their complexes with Ca2+, Na+, and K+ to obtain a set of molecular electronic properties and to correlate these properties with biological activity. According to density-functional theory (DFT) modeling, Ca2+ ions were more effectively bound by these compounds versus Na+ and K+. The DFT-optimized structures of the ligand-Ca2+ complexes and quantitative structure-activity relationship (QSAR) analysis showed that the carbonyl oxygen atoms of the N,N’-diacylated diaza-crown ethers participated in cation binding and could play an important role in Ca2+ transfer. Thus, our modeling experiments provide a molecular basis to explain at least part of the ionophore mechanism of biological action of aza-crown ethers. | ||
| 461 | _tMolecules | ||
| 463 |
_tVol. 26, iss. 8 _v[2225, 26 p.] _d2021 |
||
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aaza-crown ether | |
| 610 | 1 | _aneutrophil | |
| 610 | 1 | _aionophore | |
| 610 | 1 | _adensity-functional theory (DFT) | |
| 610 | 1 | _aquantitative structure-activity relationship (QSAR) modeling | |
| 701 | 1 |
_aBasok _bS. S. _gStepan |
|
| 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 |
_aKhlebnikov _bA. I. _cChemist _cProfessor of Tomsk Polytechnic University _f1963- _gAndrey Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\33927 |
|
| 701 | 1 |
_aLutsyuk _bA. F. _gAnatoly Fedorovich |
|
| 701 | 1 |
_aKirichenko _bT. I. _gTatjyana Ivanovna |
|
| 701 | 1 |
_aKirpotina _bL. N. _gLiliya Nikolaevna |
|
| 701 | 1 |
_aPavlovsky _bV. I. _cchemist _cProfessor of Tomsk Polytechnic University, Doctor of chemical sciences _f1958- _gViktor Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\46884 |
|
| 701 | 1 |
_aLeonov _bK. A. _gKlim Andreevich |
|
| 701 | 1 |
_aVishenkova _bD. A. _cchemist _cengineer of Tomsk Polytechnic University _f1989- _gDariya Aleksandrovna _2stltpush _3(RuTPU)RU\TPU\pers\33918 |
|
| 701 | 1 |
_aQuinn _bM. T. _gMark |
|
| 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 |
| 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 _c20210604 _gRCR |
|
| 856 | 4 | 0 | _uhttps://doi.org/10.3390/molecules26082225 |
| 942 | _cCF | ||