Synthesis and Evaluation of Chiral Rhodanine Derivatives Bearing Quinoxalinyl Imidazole Moiety as ALK5 Inhibitors / Li-Min Zhao, Fang Yan Guo, Hui Min Wang, Tong Dou, Jun Da Qi, Wen Bo Xu, Lianxun Piao, Xuejun Jin, Fen-Er Chen, Hu-Ri Piao, Chang Ji Zheng, Cheng Hua Jin
Background: TGF-β signaling pathway inhibition is considered an effective way to prevent the development of several diseases. In the design and synthesis of TGF-β inhibitors, a rhodanine compound containing a quinoxalinyl imidazole moiety was found to have strong antimicrobial activity. Objective: The purpose of this work was to investigate the antimicrobial activity of other chiral rhodanine TGF-β inhibitors synthesized. Methods: Two series of 3-substituted-5-(5-(6-methylpyridin-2-yl)-4-(quinoxalinyl-6-yl)- 1Himidazol- 2-yl)methylene)-2-thioxothiazolin-4-ones (12a-h and 13a-e) were synthesized and evaluated for their ALK5 inhibitory and antimicrobial activity. The structures were confirmed by their 1 H NMR, 13 C NMR and HRMS spectra. All the synthesized compounds were screened against Grampositive strains, Gram-negative strains, and fungi. Results: Among the synthesized compounds, compound 12h showed the highest activity (IC50 = 0.416 μM) against ALK5 kinase. Compound 12h exhibited a good selectivity index of >24 against p38α MAP kinase and was 6.0-fold more selective than the clinical candidate, compound 2 (LY- 2157299). Nearly all the compounds displayed high selectivity toward both Gram-positive and Gram-negative bacteria. They also showed similar or 2.0-fold greater antifungal activity (minimum inhibitory concentration [MIC] = 0.5 μg/mL) compared with the positive control compounds Gatifloxacin (MIC = 0.5 μg/mL) and fluconazole (MIC = 1 μg/mL). Conclusion: The findings suggest that the synthesized rhodanine compounds have good ALK5 inhibitory activity, and merit further research and development as potential antifungal drugs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Medicinal chemistry - 18(2022), 4, Seite 12 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Li-Min [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Umfang: |
1 Online-Ressource (12 p) |
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KFL011179635 |
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| 520 | |a Background: TGF-β signaling pathway inhibition is considered an effective way to prevent the development of several diseases. In the design and synthesis of TGF-β inhibitors, a rhodanine compound containing a quinoxalinyl imidazole moiety was found to have strong antimicrobial activity. Objective: The purpose of this work was to investigate the antimicrobial activity of other chiral rhodanine TGF-β inhibitors synthesized. Methods: Two series of 3-substituted-5-(5-(6-methylpyridin-2-yl)-4-(quinoxalinyl-6-yl)- 1Himidazol- 2-yl)methylene)-2-thioxothiazolin-4-ones (12a-h and 13a-e) were synthesized and evaluated for their ALK5 inhibitory and antimicrobial activity. The structures were confirmed by their 1 H NMR, 13 C NMR and HRMS spectra. All the synthesized compounds were screened against Grampositive strains, Gram-negative strains, and fungi. Results: Among the synthesized compounds, compound 12h showed the highest activity (IC50 = 0.416 μM) against ALK5 kinase. Compound 12h exhibited a good selectivity index of >24 against p38α MAP kinase and was 6.0-fold more selective than the clinical candidate, compound 2 (LY- 2157299). Nearly all the compounds displayed high selectivity toward both Gram-positive and Gram-negative bacteria. They also showed similar or 2.0-fold greater antifungal activity (minimum inhibitory concentration [MIC] = 0.5 μg/mL) compared with the positive control compounds Gatifloxacin (MIC = 0.5 μg/mL) and fluconazole (MIC = 1 μg/mL). Conclusion: The findings suggest that the synthesized rhodanine compounds have good ALK5 inhibitory activity, and merit further research and development as potential antifungal drugs | ||
| 700 | 1 | |a Guo, Fang Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hui Min |e verfasserin |4 aut | |
| 700 | 1 | |a Dou, Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Da Qi, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Wen Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Piao, Lianxun |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Xuejun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Fen-Er |e verfasserin |4 aut | |
| 700 | 1 | |a Piao, Hu-Ri |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Chang Ji |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Cheng Hua |e verfasserin |4 aut | |
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