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

Abstract

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 microM) while EPA-SOs and PID-SOs bearing an imidazolidin-2,5-dione moiety are mostly not active, exhibiting antiproliferative activity over 100 microM. 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.