Identification of benzothiazole derived monosaccharides as potent, selective, and orally bioavailable inhibitors of human and mouse galectin-3; a rare example of using a S···O binding interaction for drug design
Copyright © 2024 Elsevier Ltd. All rights reserved..
As a result of our continued efforts to pursue Gal-3 inhibitors that could be used to fully evaluate the potential of Gal-3 as a therapeutic target, two novel series of benzothiazole derived monosaccharides as potent (against both human and mouse Gal-3) and orally bioavailable Gal-3 inhibitors, represented by 4 and 5, respectively, were identified. These discoveries were made based on proposals that the benzothiazole sulfur atom could interact with the carbonyl oxygen of G182/G196 in h/mGal-3, and that the anomeric triazole moiety could be modified into an N-methyl carboxamide functionality. The interaction between the benzothiazole sulfur and the carbonyl oxygen of G196 in mGal-3 was confirmed by an X-ray co-crystal structure of early lead 9, providing a rare example of using a S···O binding interaction for drug design. It was found that for both the series, methylation of 3-OH in the monosaccharides caused no loss in h & mGal-3 potencies but significantly improved permeability of the molecules.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:101 |
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| Enthalten in: |
Bioorganic & medicinal chemistry - 101(2024) vom: 01. März, Seite 117638 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Chunjian [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmc.2024.117638 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Liu, Chunjian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of benzothiazole derived monosaccharides as potent, selective, and orally bioavailable inhibitors of human and mouse galectin-3; a rare example of using a S···O binding interaction for drug design |
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| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
| 520 | |a As a result of our continued efforts to pursue Gal-3 inhibitors that could be used to fully evaluate the potential of Gal-3 as a therapeutic target, two novel series of benzothiazole derived monosaccharides as potent (against both human and mouse Gal-3) and orally bioavailable Gal-3 inhibitors, represented by 4 and 5, respectively, were identified. These discoveries were made based on proposals that the benzothiazole sulfur atom could interact with the carbonyl oxygen of G182/G196 in h/mGal-3, and that the anomeric triazole moiety could be modified into an N-methyl carboxamide functionality. The interaction between the benzothiazole sulfur and the carbonyl oxygen of G196 in mGal-3 was confirmed by an X-ray co-crystal structure of early lead 9, providing a rare example of using a S···O binding interaction for drug design. It was found that for both the series, methylation of 3-OH in the monosaccharides caused no loss in h & mGal-3 potencies but significantly improved permeability of the molecules | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Benzothiazole | |
| 650 | 4 | |a Galectin-3 (Gal-3) | |
| 650 | 4 | |a Galectin-3 (Gal-3) inhibitor | |
| 650 | 4 | |a Interaction between sulfur and carbonyl oxygen atoms | |
| 650 | 4 | |a Monosaccharide galectin-3 (Gal-3) inhibitor | |
| 650 | 4 | |a X-ray co-crystal structure with Galectin-3 (Gal-3) | |
| 650 | 7 | |a Benzothiazoles |2 NLM | |
| 650 | 7 | |a Galectin 3 |2 NLM | |
| 650 | 7 | |a Galectins |2 NLM | |
| 650 | 7 | |a Monosaccharides |2 NLM | |
| 650 | 7 | |a Oxygen |2 NLM | |
| 650 | 7 | |a S88TT14065 |2 NLM | |
| 650 | 7 | |a Sulfur |2 NLM | |
| 650 | 7 | |a 70FD1KFU70 |2 NLM | |
| 700 | 1 | |a Wang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Jianxin |e verfasserin |4 aut | |
| 700 | 1 | |a Beno, Brett |e verfasserin |4 aut | |
| 700 | 1 | |a Raja, Thiruvenkadam |e verfasserin |4 aut | |
| 700 | 1 | |a Swidorski, Jacob |e verfasserin |4 aut | |
| 700 | 1 | |a Manepalli, Raju K V L P |e verfasserin |4 aut | |
| 700 | 1 | |a Vetrichelvan, Muthalagu |e verfasserin |4 aut | |
| 700 | 1 | |a Rao Jalagam, Prasada |e verfasserin |4 aut | |
| 700 | 1 | |a Nair, Satheesh K |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Anuradha |e verfasserin |4 aut | |
| 700 | 1 | |a Panda, Manoranjan |e verfasserin |4 aut | |
| 700 | 1 | |a Ghosh, Kaushik |e verfasserin |4 aut | |
| 700 | 1 | |a Kaushikkumar Shukla, Jinal |e verfasserin |4 aut | |
| 700 | 1 | |a Sale, Harinath |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Devang |e verfasserin |4 aut | |
| 700 | 1 | |a Singh Gautam, Shashyendra |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Dipal |e verfasserin |4 aut | |
| 700 | 1 | |a Mathur, Arvind |e verfasserin |4 aut | |
| 700 | 1 | |a Ellsworth, Bruce A |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Regueiro-Ren, Alicia |e verfasserin |4 aut | |
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