Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction
Recent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-triazoles as moderately potent inhibitors of this in...
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Elsevier
2014
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| Online Access: | https://eprints.nottingham.ac.uk/40928/ |
| _version_ | 1848796164813488128 |
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| author | Reddy, Tummala R.K. Li, Chan Guo, Xiaoxia Fischer, Peter M. Dekker, Lodewijk V. |
| author_facet | Reddy, Tummala R.K. Li, Chan Guo, Xiaoxia Fischer, Peter M. Dekker, Lodewijk V. |
| author_sort | Reddy, Tummala R.K. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Recent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-triazoles as moderately potent inhibitors of this interaction. A series of analogues were synthesized based on the 1,2,4-triazole scaffold and were evaluated for inhibition of the annexin A2–S100A10 protein interaction in competitive binding assays. 2-[(5-{[(4,6-Dimethylpyrimidin-2-yl)sulfanyl]methyl}-4-(furan-2-ylmethyl)-4H-1,2,4-triazol-3-yl)sulfanyl]-N-[4-(propan-2-yl)phenyl]acetamide (36) showed improved potency and was shown to disrupt the native complex between annexin A2 and S100A10. |
| first_indexed | 2025-11-14T19:43:38Z |
| format | Article |
| id | nottingham-40928 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:43:38Z |
| publishDate | 2014 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-409282020-05-04T16:53:03Z https://eprints.nottingham.ac.uk/40928/ Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction Reddy, Tummala R.K. Li, Chan Guo, Xiaoxia Fischer, Peter M. Dekker, Lodewijk V. Recent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-triazoles as moderately potent inhibitors of this interaction. A series of analogues were synthesized based on the 1,2,4-triazole scaffold and were evaluated for inhibition of the annexin A2–S100A10 protein interaction in competitive binding assays. 2-[(5-{[(4,6-Dimethylpyrimidin-2-yl)sulfanyl]methyl}-4-(furan-2-ylmethyl)-4H-1,2,4-triazol-3-yl)sulfanyl]-N-[4-(propan-2-yl)phenyl]acetamide (36) showed improved potency and was shown to disrupt the native complex between annexin A2 and S100A10. Elsevier 2014-10-01 Article PeerReviewed Reddy, Tummala R.K., Li, Chan, Guo, Xiaoxia, Fischer, Peter M. and Dekker, Lodewijk V. (2014) Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction. Bioorganic and Medicinal Chemistry, 22 (19). pp. 5378-5391. ISSN 1464-3391 S100 proteins; Annexins; Docking; Triazole http://www.sciencedirect.com/science/article/pii/S0968089614005598 doi:10.1016/j.bmc.2014.07.043 doi:10.1016/j.bmc.2014.07.043 |
| spellingShingle | S100 proteins; Annexins; Docking; Triazole Reddy, Tummala R.K. Li, Chan Guo, Xiaoxia Fischer, Peter M. Dekker, Lodewijk V. Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction |
| title | Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction |
| title_full | Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction |
| title_fullStr | Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction |
| title_full_unstemmed | Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction |
| title_short | Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction |
| title_sort | design, synthesis and sar exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin a2–s100a10 protein interaction |
| topic | S100 proteins; Annexins; Docking; Triazole |
| url | https://eprints.nottingham.ac.uk/40928/ https://eprints.nottingham.ac.uk/40928/ https://eprints.nottingham.ac.uk/40928/ |