Synthesis of new compounds in the series of aryl-substituted ureas with cytotoxic and antioxidant activity

Anti-Proliferative and Cytoprotective Activity of Aryl Carbamate and Aryl Urea Derivatives with Alkyl Groups and Chlorine as Substituents

“…The compounds were designed to fill the gap in the known synthetic analogs of the substituted cytokinin-like derivatives. This research continues our earlier study [ 19 ], extending it with novel compounds and data on the activity mechanisms. The task looked promising as such compounds are known for exerting cytoprotective and antitumor activity.…”

“…However, III f in the latter experiment setting stimulated cell proliferation in SH-SY5Y. Such pro-proliferative activity is quite typical for the cytokinin analogs [ 5 , 19 , 22 , 23 ].…”

“…Aryl ureas and aryl carbamates ( Table 1 ) were produced by the reaction of corresponding aryl isocyanates with imidazolidinone-substituted alcohol or amine in the presence of triethylamine in anhydrous toluene (for aryl ureas) or acetonitrile (for aryl carbamates) as described in the literature [ 19 ]. Oxalylaryl carbamates were obtained in the same way as described in refs.…”

“…Based on the data on the cytoprotective activity of the structurally similar compounds [ 5 , 19 , 22 , 23 ], we tested the synthesized compounds in two antioxidant models (protection against the H 2 O 2 and CoCl 2 cytotoxicity) in a 24 h incubation. In addition, we evaluated the analogs of EDU III for their ability to stimulate cell proliferation after a 72 h treatment.…”

“…These compounds were found to be cytotoxic to the breast cancer cell line MDA-MB-231, glioblastoma U-87 MG and neuroblastoma SH-SY5Y, but not to the melanoma A-375 cell line. The introduction of chlorine into the aromatic ring of cytokinin analogues significantly reduced the cytotoxicity, but at the same time provided the capability to protect cells from oxidative stress induced by H 2 O 2 [ 19 ]. The observed cytotoxicity was quite low (EC 50 of about 100 µM) but, given the scarcity of the data, there was a high probability that there could be more active compounds among other similar cytokinin analogs.…”