Discovery of nitroaryl urea derivatives with antiproliferative properties

Abstract

A series of urea derivatives bearing nitroaryl moiety has been synthesized and assayed for their potential antiproliferative activities. Some of the tested compounds displayed activity in RK33 laryngeal cancer cells and TE671 rhabdomyosarcoma cells while being generally less toxic to healthy HSF human fibroblasts cells. One compound was demonstrated to be a moderate CDK2 inhibitor with IC 50 ¼ 14.3 mM. Its structure was solved by an X-ray crystallography and molecular modelling was performed to determine structure-activity relationship. Obtained compounds constitute novel structures and generally demonstrated greater cytotoxicity in comparison to cisplatin. This study offers new structural motifs with potential for further development.

Synthesis, Structural Studies and Molecular Modelling of a Novel Imidazoline Derivative with Antifungal Activity

“…During the course of another investigation [13] we studied novel urea derivatives with antiproliferative properties. Having accounted for their cytotoxicity and consequently the need for protection of the natural microbiological flora we deemed it necessary to check how they influence survival of different microorganisms.…”

Palladium‐Catalyzed Synthesis of Symmetrical and Unsymmetrical Ureas Using Chromium Hexacarbonyl as a Convenient and Safe Alternative Carbonyl Source

“…They can also be used as efficient organocatalysts or ligands for transition metals . Recently Wrobel et al discovered the nitroaryl urea derivatives with antiproliferative properties (Figure a) . compound b is one of the multi‐target inhibitors with antiangiogenic and immunomodulatory properties reported by Falomir et al (Figure ) …”

Pharmacophore-based virtual screening, synthesis, biological evaluation, and molecular docking study of novel pyrrolizines bearing urea/thiourea moieties with potential cytotoxicity and CDK inhibitory activities

“…On the other hand, compound 8 was reported with moderate inhibitory activity against CDK-2 (IC 50 ¼ 14.3 lM) 21 . However, extending the chemical structure of the diaryl urea 9 with methyl piperazine and aminopyrimidine moieties allowed the new compound to occupy a larger volume of the active site of CDK-2, Figure 2.…”

“…In addition, several CDKIs were designed bearing substituted urea moiety [19][20][21][22] . The importance of this moiety in the formation of hydrogen bonding network with the kinase domain which improves inhibitory activities against CDKs was discussed in several reports 19,21,22 . Honma et al investigated the inhibitory activities of several diaryl urea derivatives against CDK-4 19 .…”