Synthesis and anti-liver fibrosis activity of imidazole and thiazole compounds containing amino acids
Copyright © 2024 Elsevier Masson SAS. All rights reserved..
Four series of imidazoles (15a-g, 20c, and 20d) and thiazoles (18a-g, 22a, and 22b) possessing various amino acids were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. Among them, compounds 15g and 18c showed the highest inhibitory activity against ALK5, with IC50 values of 0.017 and 0.025 μM, respectively. Compounds 15g and 18c efficiently inhibited extracellular matrix (ECM) deposition in TGF-β-induced hepatic stellate cells (HSCs), and eventually suppressed HSC activation. Moreover, compound 15g showed a good pharmacokinetic (PK) profile with a favorable half-life (t1/2 = 9.14 h). The results indicated that these compounds exhibited activity targeting ALK5 and may have potential in the treatment of liver fibrosis; thus they are worthy of further study.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:269 |
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| Enthalten in: |
European journal of medicinal chemistry - 269(2024) vom: 05. Apr., Seite 116311 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Meng, Yu-Qing [VerfasserIn] |
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| Links: |
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| Themen: |
ALK5 |
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| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 08.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2024.116311 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369977017 |
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| 245 | 1 | 0 | |a Synthesis and anti-liver fibrosis activity of imidazole and thiazole compounds containing amino acids |
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| 500 | |a Date Revised 08.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Four series of imidazoles (15a-g, 20c, and 20d) and thiazoles (18a-g, 22a, and 22b) possessing various amino acids were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. Among them, compounds 15g and 18c showed the highest inhibitory activity against ALK5, with IC50 values of 0.017 and 0.025 μM, respectively. Compounds 15g and 18c efficiently inhibited extracellular matrix (ECM) deposition in TGF-β-induced hepatic stellate cells (HSCs), and eventually suppressed HSC activation. Moreover, compound 15g showed a good pharmacokinetic (PK) profile with a favorable half-life (t1/2 = 9.14 h). The results indicated that these compounds exhibited activity targeting ALK5 and may have potential in the treatment of liver fibrosis; thus they are worthy of further study | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ALK5 | |
| 650 | 4 | |a Anti-Liver fibrosis | |
| 650 | 4 | |a Imidazole | |
| 650 | 4 | |a TGF-β | |
| 650 | 4 | |a Thiazole | |
| 650 | 7 | |a Thiazoles |2 NLM | |
| 650 | 7 | |a Amino Acids |2 NLM | |
| 650 | 7 | |a Receptors, Transforming Growth Factor beta |2 NLM | |
| 650 | 7 | |a Imidazoles |2 NLM | |
| 700 | 1 | |a Ren, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Jing-Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Fang-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Min, Jun-Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Nan, Ji-Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Quan, Ji-Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Lian, Li-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Cheng-Hua |e verfasserin |4 aut | |
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