Preparation and biological evaluation of new antimicrotubule agents: Modification of the imidazolidin-2-one moiety of phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates.

Autor: Gagné-Boulet M; Centre de recherche du CHU de Québec-Université Laval, Axe oncologie, Hôpital Saint-François d'Assise, Québec, QC, Canada.; Faculté de pharmacie, Université Laval, Pavillon Ferdinand-Vandry, Québec, QC, Canada., Bouzriba C; Centre de recherche du CHU de Québec-Université Laval, Axe oncologie, Hôpital Saint-François d'Assise, Québec, QC, Canada.; Faculté de pharmacie, Université Laval, Pavillon Ferdinand-Vandry, Québec, QC, Canada., Chavez Alvarez AC; Centre de recherche du CHU de Québec-Université Laval, Axe oncologie, Hôpital Saint-François d'Assise, Québec, QC, Canada.; Faculté de pharmacie, Université Laval, Pavillon Ferdinand-Vandry, Québec, QC, Canada.; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, Québec, QC, Canada., Fortin S; Centre de recherche du CHU de Québec-Université Laval, Axe oncologie, Hôpital Saint-François d'Assise, Québec, QC, Canada.; Faculté de pharmacie, Université Laval, Pavillon Ferdinand-Vandry, Québec, QC, Canada.
Jazyk: angličtina
Zdroj: Chemical biology & drug design [Chem Biol Drug Des] 2022 Feb; Vol. 99 (2), pp. 187-196. Date of Electronic Publication: 2021 Oct 17.
DOI: 10.1111/cbdd.13971
Abstrakt: We prepared and biologically evaluated 32 novel molecules named phenyl 4-(dioxoimidazolidin-1-yl)benzenesulfonates (PID-SOs) and ethyl 2-(3-(4-(phenoxysulfonyl)phenyl)ureido)acetates (EPA-SOs). The antiproliferative activity of PID-SOs and EPA-SOs was assessed on four cancer cell lines (HT-1080, HT-29, M21, and MCF7). The most potent PID-SOs bearing an imidazolidin-2,4-dione group show antiproliferative activity in the nanomolar to low micromolar range (0.066 - 6 µM) while EPA-SOs and PID-SOs bearing an imidazolidin-2,5-dione moiety are mostly not active, exhibiting antiproliferative activity over 100 µM. The most potent PID-SOs (16-18) arrest the cell cycle progression in G2/M phase and interact with the colchicine-binding site leading to the microtubule and cytoskeleton disruption. Moreover, their antiproliferative activity is not impaired in vinblastine-, paclitaxel-, and multidrug-resistant cell lines. Finally, our study confirms that PID-SOs bearing the imidazolidin-2,4-dione moiety are a new family of promising antimitotics.
(© 2021 John Wiley & Sons A/S.)
Databáze: MEDLINE
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