Synthesis and biological evaluation of coumarin derivatives containing oxime ester as α-glucosidase inhibitors
In this study, potent coumarin derivatives containing oxime ester 1 ∼ 28 as α-glucosidase inhibitors were developed through a stepwise structure optimization, and the structure activity relationship was uncovered. Among them, compound 20 exhibited outstanding α-glucosidase inhibitory activity with IC50 of 2.54 ± 0.04 μM compared to 640.57 ± 1.13 μM of Acarbose. Kinetic study ascertained that compound 20 was a reversible and uncompetitive α-glucosidase inhibitor. 3D fluorescence results showed that the interaction of compound 20 with α-glucosidase caused the changes of microenvironments and polypeptide backbone structure of α-glucosidase. CD spectra results revealed that compound 20 decreased the α-helix content and increased the β-sheet content. Molecular docking analysis indicated that compound 20 well located into the active site and mainly bind with Phe157, His239, His279, Tyr71, and Arg312 to reduce the catalytic activity of α-glucosidase..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Arabian Journal of Chemistry - 15(2022), 9, Seite 104072- |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Xin Zhang [VerfasserIn] |
|---|
| Links: |
doi.org [kostenfrei] |
|---|
| Themen: |
A-Glucosidase |
|---|
| doi: |
10.1016/j.arabjc.2022.104072 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
DOAJ043152384 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ043152384 | ||
| 003 | DE-627 | ||
| 005 | 20230308070508.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230227s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.arabjc.2022.104072 |2 doi | |
| 035 | |a (DE-627)DOAJ043152384 | ||
| 035 | |a (DE-599)DOAJ0bcc0d7a8aed4e9dad41955808ee80ca | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a QD1-999 | |
| 100 | 0 | |a Xin Zhang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Synthesis and biological evaluation of coumarin derivatives containing oxime ester as α-glucosidase inhibitors |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a In this study, potent coumarin derivatives containing oxime ester 1 ∼ 28 as α-glucosidase inhibitors were developed through a stepwise structure optimization, and the structure activity relationship was uncovered. Among them, compound 20 exhibited outstanding α-glucosidase inhibitory activity with IC50 of 2.54 ± 0.04 μM compared to 640.57 ± 1.13 μM of Acarbose. Kinetic study ascertained that compound 20 was a reversible and uncompetitive α-glucosidase inhibitor. 3D fluorescence results showed that the interaction of compound 20 with α-glucosidase caused the changes of microenvironments and polypeptide backbone structure of α-glucosidase. CD spectra results revealed that compound 20 decreased the α-helix content and increased the β-sheet content. Molecular docking analysis indicated that compound 20 well located into the active site and mainly bind with Phe157, His239, His279, Tyr71, and Arg312 to reduce the catalytic activity of α-glucosidase. | ||
| 650 | 4 | |a Coumarin derivatives | |
| 650 | 4 | |a a-Glucosidase | |
| 650 | 4 | |a Inhibition mechanism | |
| 650 | 4 | |a Molecular docking | |
| 653 | 0 | |a Chemistry | |
| 700 | 0 | |a Ying-Ying Zheng |e verfasserin |4 aut | |
| 700 | 0 | |a Chun-Mei Hu |e verfasserin |4 aut | |
| 700 | 0 | |a Xiao-Zheng Wu |e verfasserin |4 aut | |
| 700 | 0 | |a Jing Lin |e verfasserin |4 aut | |
| 700 | 0 | |a Zhuang Xiong |e verfasserin |4 aut | |
| 700 | 0 | |a Kun Zhang |e verfasserin |4 aut | |
| 700 | 0 | |a Xue-Tao Xu |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Arabian Journal of Chemistry |d Elsevier, 2016 |g 15(2022), 9, Seite 104072- |w (DE-627)DOAJ000039403 |x 18785352 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2022 |g number:9 |g pages:104072- |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.arabjc.2022.104072 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/0bcc0d7a8aed4e9dad41955808ee80ca |z kostenfrei |
| 856 | 4 | 0 | |u http://www.sciencedirect.com/science/article/pii/S1878535222003884 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/1878-5352 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2022 |e 9 |h 104072- | ||