p53-MDM2/MDMX interaction inhibitors represent the prospective agents for targeted anticancer therapy in tumors expressing wild-type p53 protein. Imidazoline-based MDM2-targeted inhibitors of such type, nutlins, contain halogensubstituted phenyl rings, which dramatically decrease the solubility of compounds in water. The addition of suitable hydrophilic substituents in benzene rings and to imidazoline nitrogen can improve the compound's water solubility. In this study, we have synthesized novel hydrophilic cis-2,4,5-tris(alkoxyphenyl)imidazolines and studied the influence of N-sulfonyl substituent on protein-protein interaction compared to unsubstituted alkoxy-compounds. The biological activity of the obtained compounds was studied using Western blot analysis on A549, RKO and SH-SY5Y cancer cell lines. It was found that the derivatives are able to inhibit MDM2/MDMX-p53 interaction, promote p53 stabilization and induce p21 expression in the concentrations from 500 nM.
Imidazole derivatives
Imidazole derivatives R 0190Regioselective Synthesis of cis-and trans-2,4,5-Triarylimidazolines and 2,4,5-Triarylimidazoles from Available Reagents. -Several 1,3,5-triaryl-2,4-diazapentadienes (II) are synthesized by reaction of aromatic aldehydes with ammonia and selectively transformed into the title imidazole derivatives by tBuOK-mediated ring closure reactions. -(LOZINSKAYA, N. A.; TSYBEZOVA, V. V.; PROSKURNINA*, M.; ZEFIROV, N. S.; Russ. Chem. Bull. 52 (2003) 3, 674-678; Dep. Chem., Lomonosov Moscow State Univ., Moscow 119899, Russia; Eng.) -M. Kowall 41-128
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