Modular preparation of biphenyl triazoles via click chemistry as non-competitive hyaluronidase inhibitors
Copyright © 2024 Elsevier Inc. All rights reserved..
Hyaluronidase is a promising target in drug discovery, given its overexpression in a range of physiological and pathological processes, including tumor migration, skin aging, sagging, and wrinkling, as well as inflammation and bacterial infections. In this study, to identify novel hyaluronidase inhibitors, we applied click chemistry for the modular synthesis of 370 triazoles in 96-well plates, starting with biphenyl azide. Utilizing an optimized turbidimetric screening assay in microplates, we identified Fmoc-containing triazoles 5 and 6, as well as quinoline-containing triazoles 15 and 16, as highly effective hyaluronidase inhibitors. Subsequent research indicated that these triazoles potentially interact with a novel binding site of hyaluronidase. Notably, these inhibitors displayed minimal cytotoxicity and showed promising anti-inflammatory effects in LPS-stimulated macrophages. Remarkably, compound 6 significantly reduced NO release by 74 % at a concentration of 20 μM.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:146 |
|---|---|
| Enthalten in: |
Bioorganic chemistry - 146(2024) vom: 26. Apr., Seite 107291 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Qin, Yiman [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
2L9GJK6MGN |
|---|
| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bioorg.2024.107291 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370105869 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370105869 | ||
| 003 | DE-627 | ||
| 005 | 20240415233528.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240324s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bioorg.2024.107291 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1376.xml |
| 035 | |a (DE-627)NLM370105869 | ||
| 035 | |a (NLM)38521011 | ||
| 035 | |a (PII)S0045-2068(24)00196-2 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Qin, Yiman |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Modular preparation of biphenyl triazoles via click chemistry as non-competitive hyaluronidase inhibitors |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.04.2024 | ||
| 500 | |a Date Revised 15.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a Hyaluronidase is a promising target in drug discovery, given its overexpression in a range of physiological and pathological processes, including tumor migration, skin aging, sagging, and wrinkling, as well as inflammation and bacterial infections. In this study, to identify novel hyaluronidase inhibitors, we applied click chemistry for the modular synthesis of 370 triazoles in 96-well plates, starting with biphenyl azide. Utilizing an optimized turbidimetric screening assay in microplates, we identified Fmoc-containing triazoles 5 and 6, as well as quinoline-containing triazoles 15 and 16, as highly effective hyaluronidase inhibitors. Subsequent research indicated that these triazoles potentially interact with a novel binding site of hyaluronidase. Notably, these inhibitors displayed minimal cytotoxicity and showed promising anti-inflammatory effects in LPS-stimulated macrophages. Remarkably, compound 6 significantly reduced NO release by 74 % at a concentration of 20 μM | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Biphenyl triazole | |
| 650 | 4 | |a Click chemistry | |
| 650 | 4 | |a Hyaluronidase | |
| 650 | 4 | |a Non-competitive inhibitor | |
| 650 | 7 | |a Hyaluronoglucosaminidase |2 NLM | |
| 650 | 7 | |a EC 3.2.1.35 |2 NLM | |
| 650 | 7 | |a biphenyl |2 NLM | |
| 650 | 7 | |a 2L9GJK6MGN |2 NLM | |
| 650 | 7 | |a Triazoles |2 NLM | |
| 650 | 7 | |a Biphenyl Compounds |2 NLM | |
| 700 | 1 | |a Li, Guanyi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Guangyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hongxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Pengfei |e verfasserin |4 aut | |
| 700 | 1 | |a Hua, Wentao |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yaxue |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jiong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioorganic chemistry |d 1986 |g 146(2024) vom: 26. Apr., Seite 107291 |w (DE-627)NLM012846570 |x 1090-2120 |7 nnns |
| 773 | 1 | 8 | |g volume:146 |g year:2024 |g day:26 |g month:04 |g pages:107291 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bioorg.2024.107291 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 146 |j 2024 |b 26 |c 04 |h 107291 | ||