Nanomolar potency of imidazo[2,1-b]thiazole analogs as indoleamine 2,3-dioxygenase inhibitors
© 2021 Deutsche Pharmazeutische Gesellschaft..
Novel series of imidazo[2,1-b]thiazole analogs were designed, synthesized, and biologically evaluated as indoleamine 2,3-dioxygenase (IDO1) inhibitors. Imidazo[2,1-b]thiazoles 6, 7, and 8 showed inhibitory profiles against IDO1 at IC50 values of 68.48, 82.39, and 48.48 nM, respectively, compared with IDO5L at IC50 67.40 nM. Benzo[d]imidazo[2,1-b]thiazoles 17, 20, and 22 showed promising IDO1 inhibition at IC50 values of 53.58, 53.16, and 57.95 nM, respectively. Compound 7 showed a growth-inhibitory profile at GI of 39.33% against the MCF7 breast cancer cell line, while 8 proved lethal to ACHN renal cancer cells. Cells treated with compounds 17 and 22 showed a typical apoptosis pattern of DNA fragments that reflected the G0/G1, S, and G2/M phases of the cell cycle, together with a pre-G1 phase corresponding to apoptotic cells, which indicates that cell growth arrest occurred at the S phase. Molecular modeling simulations validated the potential of benzo[d]imidazo[2,1-b]thiazole analogs to chelate iron(III) within the IDO1 binding pocket and, hence, to have a better binding affinity via hydrophobic-hydrophobic interactions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:354 |
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| Enthalten in: |
Archiv der Pharmazie - 354(2021), 11 vom: 15. Nov., Seite e2100202 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ewida, Menna A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.02.2022 Date Revised 15.02.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/ardp.202100202 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Novel series of imidazo[2,1-b]thiazole analogs were designed, synthesized, and biologically evaluated as indoleamine 2,3-dioxygenase (IDO1) inhibitors. Imidazo[2,1-b]thiazoles 6, 7, and 8 showed inhibitory profiles against IDO1 at IC50 values of 68.48, 82.39, and 48.48 nM, respectively, compared with IDO5L at IC50 67.40 nM. Benzo[d]imidazo[2,1-b]thiazoles 17, 20, and 22 showed promising IDO1 inhibition at IC50 values of 53.58, 53.16, and 57.95 nM, respectively. Compound 7 showed a growth-inhibitory profile at GI of 39.33% against the MCF7 breast cancer cell line, while 8 proved lethal to ACHN renal cancer cells. Cells treated with compounds 17 and 22 showed a typical apoptosis pattern of DNA fragments that reflected the G0/G1, S, and G2/M phases of the cell cycle, together with a pre-G1 phase corresponding to apoptotic cells, which indicates that cell growth arrest occurred at the S phase. Molecular modeling simulations validated the potential of benzo[d]imidazo[2,1-b]thiazole analogs to chelate iron(III) within the IDO1 binding pocket and, hence, to have a better binding affinity via hydrophobic-hydrophobic interactions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IDO1 inhibitors | |
| 650 | 4 | |a antitumor testing | |
| 650 | 4 | |a cell cycle analysis | |
| 650 | 4 | |a imidazo[2,1-b]thiazole | |
| 650 | 4 | |a molecular modeling simulations | |
| 650 | 4 | |a synthesis | |
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| 650 | 7 | |a Imidazoles |2 NLM | |
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| 700 | 1 | |a Ahmed, Mahmoud S |e verfasserin |4 aut | |
| 700 | 1 | |a Allam, Heba Abdelrasheed |e verfasserin |4 aut | |
| 700 | 1 | |a ElBagary, Ramzia I |e verfasserin |4 aut | |
| 700 | 1 | |a George, Riham F |e verfasserin |4 aut | |
| 700 | 1 | |a Georgey, Hanan H |e verfasserin |4 aut | |
| 700 | 1 | |a El-Subbagh, Hussein I |e verfasserin |4 aut | |
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