Tricyclic Isatin Derivatives as Anti-Inflammatory Compounds with High Kinase Binding Affinity; Molecules; Vol. 30, iss. 14
| Parent link: | Molecules.— .— Basel: MDPI AG Vol. 30, iss. 14.— 2025.— Article number 2914, 17 p. |
|---|---|
| Drugi avtorji: | , , , |
| Izvleček: | Title screen Oximes have been reported to exhibit useful pharmaceutical properties, including compounds with anticancer, anti-arthritis, antibacterial, and neuroprotective activities. Many oximes are kinase inhibitors and have been shown to inhibit various kinases. Herein, a panel of oxime derivatives of tricyclic isatins was synthesized and evaluated for inhibition of cellular inflammatory responses and binding affinity to several kinases. Compounds 5a and 5d (a.k.a. NS-102), which have an unsubstituted oxime group, inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in human THP-1Blue monocytic cells and interleukin-6 (IL-6) production in human MonoMac-6 monocytic cells, with IC50 values in the micromolar range. These compounds also inhibited LPS-induced production of several other proinflammatory cytokines, including IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF) in MonoMac-6 cells. Compounds 5a and 5d exhibited nanomolar/submicromolar binding affinity toward several kinase targets. The most potent inhibitor, 5d (3-(hydroxyimino)-5-nitro-1,3,6,7,8,9-hexahydro-2H-benzo[g]indol-2-one), demonstrated high binding affinity for 12 kinases, including DYRK1A, DYRK1B, PIM1, Haspin, HIPK1-3, IRAK1, NEK10, and DAPK1-3. Molecular modeling suggested modes of binding interaction of selected compounds in the DYRK1A and PIM1 catalytic sites that agreed with the experimental binding data. Our results demonstrate that tricyclic isatin oximes could be potential candidates for developing anti-inflammatory drugs with neuroprotective effects for treating neurodegenerative diseases Текстовый файл |
| Jezik: | angleščina |
| Izdano: |
2025
|
| Teme: | |
| Online dostop: | https://doi.org/10.3390/molecules30142914 |
| Format: | Elektronski Book Chapter |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=682269 |
MARC
| LEADER | 00000naa0a2200000 4500 | ||
|---|---|---|---|
| 001 | 682269 | ||
| 005 | 20251014112910.0 | ||
| 090 | |a 682269 | ||
| 100 | |a 20251014d2025 k||y0rusy50 ba | ||
| 101 | 0 | |a eng | |
| 102 | |a CH | ||
| 135 | |a drcn ---uucaa | ||
| 181 | 0 | |a i |b e | |
| 182 | 0 | |a b | |
| 183 | 0 | |a cr |2 RDAcarrier | |
| 200 | 1 | |a Tricyclic Isatin Derivatives as Anti-Inflammatory Compounds with High Kinase Binding Affinity |f Alexander V. Uvarov, Igor A. Schepetkin, Mark T. Quinn, Andrei I. Khlebnikov | |
| 203 | |a Текст |b визуальный |c электронный | ||
| 283 | |a online_resource |2 RDAcarrier | ||
| 300 | |a Title screen | ||
| 320 | |a References: 53 tit | ||
| 330 | |a Oximes have been reported to exhibit useful pharmaceutical properties, including compounds with anticancer, anti-arthritis, antibacterial, and neuroprotective activities. Many oximes are kinase inhibitors and have been shown to inhibit various kinases. Herein, a panel of oxime derivatives of tricyclic isatins was synthesized and evaluated for inhibition of cellular inflammatory responses and binding affinity to several kinases. Compounds 5a and 5d (a.k.a. NS-102), which have an unsubstituted oxime group, inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in human THP-1Blue monocytic cells and interleukin-6 (IL-6) production in human MonoMac-6 monocytic cells, with IC50 values in the micromolar range. These compounds also inhibited LPS-induced production of several other proinflammatory cytokines, including IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF) in MonoMac-6 cells. Compounds 5a and 5d exhibited nanomolar/submicromolar binding affinity toward several kinase targets. The most potent inhibitor, 5d (3-(hydroxyimino)-5-nitro-1,3,6,7,8,9-hexahydro-2H-benzo[g]indol-2-one), demonstrated high binding affinity for 12 kinases, including DYRK1A, DYRK1B, PIM1, Haspin, HIPK1-3, IRAK1, NEK10, and DAPK1-3. Molecular modeling suggested modes of binding interaction of selected compounds in the DYRK1A and PIM1 catalytic sites that agreed with the experimental binding data. Our results demonstrate that tricyclic isatin oximes could be potential candidates for developing anti-inflammatory drugs with neuroprotective effects for treating neurodegenerative diseases | ||
| 336 | |a Текстовый файл | ||
| 461 | 1 | |t Molecules |c Basel |n MDPI AG | |
| 463 | 1 | |t Vol. 30, iss. 14 |v Article number 2914, 17 p. |d 2025 | |
| 610 | 1 | |a dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) | |
| 610 | 1 | |a proviral insertion site in Moloney murine leukemia virus (PIM) | |
| 610 | 1 | |a isatin; aryl oxime | |
| 610 | 1 | |a NS-102 | |
| 610 | 1 | |a anti-inflammatory | |
| 610 | 1 | |a cytokine | |
| 610 | 1 | |a электронный ресурс | |
| 610 | 1 | |a труды учёных ТПУ | |
| 701 | 1 | |a Uvarov |b A. V. |g Aleksandr Valerjevich | |
| 701 | 1 | |a Schepetkin |b I. A. |g Igor | |
| 701 | 1 | |a Quinn |b M. T. |g Mark | |
| 701 | 1 | |a Khlebnikov |b A. I. |c Chemist |c Professor of Tomsk Polytechnic University |f 1963- |g Andrey Ivanovich |9 17500 | |
| 801 | 0 | |a RU |b 63413507 |c 20251014 | |
| 850 | |a 63413507 | ||
| 856 | 4 | |u https://doi.org/10.3390/molecules30142914 |z https://doi.org/10.3390/molecules30142914 | |
| 942 | |c CF | ||