Modification of the phenyl ring B of phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates by pyridinyl moiety leads to novel antimitotics targeting the colchicine-binding site
Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved..
A series of 8 novel pyridinyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PYRIB-SOs) were designed, prepared and evaluated for their mechanism of action. PYRIB-SOs were found to have antiproliferative activity in the nanomolar to submicromolar range on several breast cancer cell lines. Moreover, subsequent biofunctional assays indicated that the most potent PYRIB-SOs 1-3 act as antimitotics binding to the colchicine-binding site (C-BS) of α, β-tubulin and that they arrest the cell cycle progression in the G2/M phase. Microtubule immunofluorescence and tubulin polymerisation assay confirm that they disrupt the cytoskeleton through inhibition of tubulin polymerisation as observed with microtubule-destabilising agents. They also show good overall theoretical physicochemical, pharmacokinetic and druglike properties. Overall, these results show that PYRIB-SOs is a new family of promising antimitotics to be further studied in vivo for biopharmaceutical and pharmacodynamic evaluations.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:105 |
|---|---|
| Enthalten in: |
Bioorganic & medicinal chemistry letters - 105(2024) vom: 01. Apr., Seite 129745 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ouellette, Vincent [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 27.04.2024 Date Revised 27.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bmcl.2024.129745 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM371034655 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM371034655 | ||
| 003 | DE-627 | ||
| 005 | 20240428232032.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240415s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bmcl.2024.129745 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1391.xml |
| 035 | |a (DE-627)NLM371034655 | ||
| 035 | |a (NLM)38614151 | ||
| 035 | |a (PII)S0960-894X(24)00147-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ouellette, Vincent |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Modification of the phenyl ring B of phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates by pyridinyl moiety leads to novel antimitotics targeting the colchicine-binding site |
| 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 27.04.2024 | ||
| 500 | |a Date Revised 27.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a A series of 8 novel pyridinyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PYRIB-SOs) were designed, prepared and evaluated for their mechanism of action. PYRIB-SOs were found to have antiproliferative activity in the nanomolar to submicromolar range on several breast cancer cell lines. Moreover, subsequent biofunctional assays indicated that the most potent PYRIB-SOs 1-3 act as antimitotics binding to the colchicine-binding site (C-BS) of α, β-tubulin and that they arrest the cell cycle progression in the G2/M phase. Microtubule immunofluorescence and tubulin polymerisation assay confirm that they disrupt the cytoskeleton through inhibition of tubulin polymerisation as observed with microtubule-destabilising agents. They also show good overall theoretical physicochemical, pharmacokinetic and druglike properties. Overall, these results show that PYRIB-SOs is a new family of promising antimitotics to be further studied in vivo for biopharmaceutical and pharmacodynamic evaluations | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Anticancer agents | |
| 650 | 4 | |a Antimicrotubule agents | |
| 650 | 4 | |a Antimitotics | |
| 650 | 4 | |a Colchicine-binding site ligands | |
| 650 | 4 | |a PYRIB-SOs | |
| 650 | 4 | |a Pyridinyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates | |
| 650 | 7 | |a Colchicine |2 NLM | |
| 650 | 7 | |a SML2Y3J35T |2 NLM | |
| 650 | 7 | |a Antimitotic Agents |2 NLM | |
| 650 | 7 | |a Benzenesulfonates |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Tubulin |2 NLM | |
| 650 | 7 | |a Tubulin Modulators |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 700 | 1 | |a Bouzriba, Chahrazed |e verfasserin |4 aut | |
| 700 | 1 | |a Chavez Alvarez, Atziri Corin |e verfasserin |4 aut | |
| 700 | 1 | |a Hamel-Côté, Geneviève |e verfasserin |4 aut | |
| 700 | 1 | |a Fortin, Sébastien |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioorganic & medicinal chemistry letters |d 1992 |g 105(2024) vom: 01. Apr., Seite 129745 |w (DE-627)NLM09063828X |x 1464-3405 |7 nnns |
| 773 | 1 | 8 | |g volume:105 |g year:2024 |g day:01 |g month:04 |g pages:129745 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bmcl.2024.129745 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 105 |j 2024 |b 01 |c 04 |h 129745 | ||