Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential
Oximes have been studied for decades because of their significant roles as acetylcholinesterase reactivators. Over the last twenty years, a large number of oximes have been reported with useful pharmaceutical properties, including compounds with antibacterial, anticancer, anti-arthritis, and anti-st...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/6/777 |
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| author | Igor A. Schepetkin Mark B. Plotnikov Andrei I. Khlebnikov Tatiana M. Plotnikova Mark T. Quinn |
| author_facet | Igor A. Schepetkin Mark B. Plotnikov Andrei I. Khlebnikov Tatiana M. Plotnikova Mark T. Quinn |
| author_sort | Igor A. Schepetkin |
| collection | DOAJ |
| description | Oximes have been studied for decades because of their significant roles as acetylcholinesterase reactivators. Over the last twenty years, a large number of oximes have been reported with useful pharmaceutical properties, including compounds with antibacterial, anticancer, anti-arthritis, and anti-stroke activities. Many oximes are kinase inhibitors and have been shown to inhibit over 40 different kinases, including AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K), cyclin-dependent kinase (CDK), serine/threonine kinases glycogen synthase kinase 3 α/β (GSK-3α/β), Aurora A, B-Raf, Chk1, death-associated protein-kinase-related 2 (DRAK2), phosphorylase kinase (PhK), serum and glucocorticoid-regulated kinase (SGK), Janus tyrosine kinase (JAK), and multiple receptor and non-receptor tyrosine kinases. Some oximes are inhibitors of lipoxygenase 5, human neutrophil elastase, and proteinase 3. The oxime group contains two H-bond acceptors (nitrogen and oxygen atoms) and one H-bond donor (OH group), versus only one H-bond acceptor present in carbonyl groups. This feature, together with the high polarity of oxime groups, may lead to a significantly different mode of interaction with receptor binding sites compared to corresponding carbonyl compounds, despite small changes in the total size and shape of the compound. In addition, oximes can generate nitric oxide. This review is focused on oximes as kinase inhibitors with anticancer and anti-inflammatory activities. Oximes with non-kinase targets or mechanisms of anti-inflammatory activity are also discussed. |
| first_indexed | 2024-03-10T11:09:08Z |
| format | Article |
| id | doaj.art-36c66d7cc8074103a1a8b9a79a8cabb2 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T11:09:08Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-36c66d7cc8074103a1a8b9a79a8cabb22023-11-21T20:53:16ZengMDPI AGBiomolecules2218-273X2021-05-0111677710.3390/biom11060777Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory PotentialIgor A. Schepetkin0Mark B. Plotnikov1Andrei I. Khlebnikov2Tatiana M. Plotnikova3Mark T. Quinn4Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USAGoldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, RussiaKizhner Research Center, National Research Tomsk Polytechnic University, 634050 Tomsk, RussiaDepartment of Pharmacology, Siberian State Medical University, 634050 Tomsk, RussiaDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USAOximes have been studied for decades because of their significant roles as acetylcholinesterase reactivators. Over the last twenty years, a large number of oximes have been reported with useful pharmaceutical properties, including compounds with antibacterial, anticancer, anti-arthritis, and anti-stroke activities. Many oximes are kinase inhibitors and have been shown to inhibit over 40 different kinases, including AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K), cyclin-dependent kinase (CDK), serine/threonine kinases glycogen synthase kinase 3 α/β (GSK-3α/β), Aurora A, B-Raf, Chk1, death-associated protein-kinase-related 2 (DRAK2), phosphorylase kinase (PhK), serum and glucocorticoid-regulated kinase (SGK), Janus tyrosine kinase (JAK), and multiple receptor and non-receptor tyrosine kinases. Some oximes are inhibitors of lipoxygenase 5, human neutrophil elastase, and proteinase 3. The oxime group contains two H-bond acceptors (nitrogen and oxygen atoms) and one H-bond donor (OH group), versus only one H-bond acceptor present in carbonyl groups. This feature, together with the high polarity of oxime groups, may lead to a significantly different mode of interaction with receptor binding sites compared to corresponding carbonyl compounds, despite small changes in the total size and shape of the compound. In addition, oximes can generate nitric oxide. This review is focused on oximes as kinase inhibitors with anticancer and anti-inflammatory activities. Oximes with non-kinase targets or mechanisms of anti-inflammatory activity are also discussed.https://www.mdpi.com/2218-273X/11/6/777oximekinase inhibitorindirubinnitric oxidemolecular modelinginflammation |
| spellingShingle | Igor A. Schepetkin Mark B. Plotnikov Andrei I. Khlebnikov Tatiana M. Plotnikova Mark T. Quinn Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential Biomolecules oxime kinase inhibitor indirubin nitric oxide molecular modeling inflammation |
| title | Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential |
| title_full | Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential |
| title_fullStr | Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential |
| title_full_unstemmed | Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential |
| title_short | Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential |
| title_sort | oximes novel therapeutics with anticancer and anti inflammatory potential |
| topic | oxime kinase inhibitor indirubin nitric oxide molecular modeling inflammation |
| url | https://www.mdpi.com/2218-273X/11/6/777 |
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