Discovery of novel urea derivatives as ferroptosis and autophagy inducer for human colon cancer treatment
Copyright © 2024 Elsevier Masson SAS. All rights reserved..
A series of novel urea derivatives were designed, synthesized and evaluated for their inhibitory activities against HT-29 cells, and structure-activity relationships (SAR) were summarized. Compound 10p stood out from these derivatives, exhibiting the most potent antiproliferative activity. Further biological studies demonstrated that 10p arrested cell cycle at G2/M phase via regulating cell cycle-related proteins CDK1 and Cyclin B1. The underlying molecular mechanisms demonstrated that 10p induced cell death through ferroptosis and autophagy, but not apoptosis. Moreover, 10p-induced ferroptosis and autophagy were both related with accumulation of ROS, but they were independent of each other. Our findings substantiated that 10p combines ferroptosis induction and autophagy trigger in single molecule, making it a potential candidate for colon cancer treatment and is worth further development.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:268 |
|---|---|
| Enthalten in: |
European journal of medicinal chemistry - 268(2024) vom: 15. März, Seite 116277 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liang, Tingting [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Autophagy |
|---|
| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 18.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ejmech.2024.116277 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369125975 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369125975 | ||
| 003 | DE-627 | ||
| 005 | 20240318234529.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240301s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejmech.2024.116277 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1334.xml |
| 035 | |a (DE-627)NLM369125975 | ||
| 035 | |a (NLM)38422700 | ||
| 035 | |a (PII)S0223-5234(24)00157-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liang, Tingting |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Discovery of novel urea derivatives as ferroptosis and autophagy inducer for human colon cancer treatment |
| 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 18.03.2024 | ||
| 500 | |a Date Revised 18.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a A series of novel urea derivatives were designed, synthesized and evaluated for their inhibitory activities against HT-29 cells, and structure-activity relationships (SAR) were summarized. Compound 10p stood out from these derivatives, exhibiting the most potent antiproliferative activity. Further biological studies demonstrated that 10p arrested cell cycle at G2/M phase via regulating cell cycle-related proteins CDK1 and Cyclin B1. The underlying molecular mechanisms demonstrated that 10p induced cell death through ferroptosis and autophagy, but not apoptosis. Moreover, 10p-induced ferroptosis and autophagy were both related with accumulation of ROS, but they were independent of each other. Our findings substantiated that 10p combines ferroptosis induction and autophagy trigger in single molecule, making it a potential candidate for colon cancer treatment and is worth further development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a Colon cancer | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Urea derivatives | |
| 650 | 7 | |a Cell Cycle Proteins |2 NLM | |
| 700 | 1 | |a Dong, Haiyang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhuangzhuang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Xueting |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Jianguo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yahong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianhong |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Guanhua |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of medicinal chemistry |d 1994 |g 268(2024) vom: 15. März, Seite 116277 |w (DE-627)NLM106608835 |x 1768-3254 |7 nnns |
| 773 | 1 | 8 | |g volume:268 |g year:2024 |g day:15 |g month:03 |g pages:116277 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejmech.2024.116277 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 268 |j 2024 |b 15 |c 03 |h 116277 | ||