Design, synthesis, and biological evaluation of new biaryl derivatives of cycloalkyl diacetamide bearing chalcone moiety as type II c-MET kinase inhibitors
© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG..
Many human cancers have been associated with the deregulation of the mesenchymal-epithelial transition factor tyrosine kinase (MET) receptor, a promising drug target for anticancer drug discovery. Herein, we report the discovery of a novel structure of potent chalcone-based derivatives type II c-Met inhibitors which are comparable to Foretinib (IC50 = 14 nM) as a potent reference drug. Based on our design strategy, we also expected an anti-tubulin activity for the compounds. However, the weak inhibitory effects on microtubules were confirmed by cell cycle analyses implicated that the observed cytotoxicity against HeLa cells probably was not derived from tubulin inhibition. Compounds 14q and 14k with IC50 values of 24 nM and 45 nM, respectively, demonstrated favorable inhibition of MET kinase activity, and desirable bonding interactions in the ligand-MET enzyme complex stability in molecular docking studies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Molecular diversity - (2024) vom: 11. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Salarinejad, Somayeh [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Anticancer |
|---|
| Anmerkungen: |
Date Revised 11.03.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1007/s11030-024-10807-x |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36956281X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36956281X | ||
| 003 | DE-627 | ||
| 005 | 20240312234536.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240312s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s11030-024-10807-x |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1324.xml |
| 035 | |a (DE-627)NLM36956281X | ||
| 035 | |a (NLM)38466553 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Salarinejad, Somayeh |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Design, synthesis, and biological evaluation of new biaryl derivatives of cycloalkyl diacetamide bearing chalcone moiety as type II c-MET kinase 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 Revised 11.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. | ||
| 520 | |a Many human cancers have been associated with the deregulation of the mesenchymal-epithelial transition factor tyrosine kinase (MET) receptor, a promising drug target for anticancer drug discovery. Herein, we report the discovery of a novel structure of potent chalcone-based derivatives type II c-Met inhibitors which are comparable to Foretinib (IC50 = 14 nM) as a potent reference drug. Based on our design strategy, we also expected an anti-tubulin activity for the compounds. However, the weak inhibitory effects on microtubules were confirmed by cell cycle analyses implicated that the observed cytotoxicity against HeLa cells probably was not derived from tubulin inhibition. Compounds 14q and 14k with IC50 values of 24 nM and 45 nM, respectively, demonstrated favorable inhibition of MET kinase activity, and desirable bonding interactions in the ligand-MET enzyme complex stability in molecular docking studies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anticancer | |
| 650 | 4 | |a Chalcone | |
| 650 | 4 | |a Dicarboxamide | |
| 650 | 4 | |a Tubulin polymerization | |
| 650 | 4 | |a c-MET Kinase | |
| 700 | 1 | |a Seyfi, Soheila |e verfasserin |4 aut | |
| 700 | 1 | |a Hayashi, Seiko |e verfasserin |4 aut | |
| 700 | 1 | |a Moghimi, Setareh |e verfasserin |4 aut | |
| 700 | 1 | |a Toolabi, Mahsa |e verfasserin |4 aut | |
| 700 | 1 | |a Taslimi, Parham |e verfasserin |4 aut | |
| 700 | 1 | |a Firoozpour, Loghman |e verfasserin |4 aut | |
| 700 | 1 | |a Usui, Takeo |e verfasserin |4 aut | |
| 700 | 1 | |a Foroumadi, Alireza |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular diversity |d 1997 |g (2024) vom: 11. März |w (DE-627)NLM091914590 |x 1573-501X |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:11 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s11030-024-10807-x |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 11 |c 03 | ||