Arylurea Derivatives: A Class of Potential Cancer Targeting Agents

Chen, Jia-Nian; Wu, De-Wen; Li, Ting; Yang, Kang-Jian; Li, Cheng; Zhou, Zuping; Pu, Shiming; Lin, Wenchu

doi:10.2174/1568026617666170707123553

Cited by 8 publications

(2 citation statements)

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“…Pyridyl urea I c was also anti-proliferative, with some preference toward the melanoma and breast cancer cell line ( Figure 4 ). The observed activity was in line with the already described in the literature [ 29 ].…”

Section: Discussionsupporting

confidence: 92%

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

Oshchepkov

Kovalenko²,

Kalistratova³

et al. 2022

Molecules

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Natural cytokinines are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of aryl carbamate, pyridyl urea, and aryl urea cytokinine analogs with alkyl and chlorine substitutions and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Aryl carbamates with the oxamate moiety were selectively anti-proliferative for the cancer cell lines tested, while the aryl ureas were inactive. In the cytoprotection studies, the same aryl carbamates were able to counteract the CoCl2 cytotoxicity by 3–8%. The possible molecular targets of the aryl carbamates during the anti-proliferative action were the adenosine A2 receptor and CDK2. The obtained results are promising for the development of novel anti-cancer therapeutics.

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Section: Discussionsupporting

confidence: 92%

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

Oshchepkov

Kovalenko²,

Kalistratova³

et al. 2022

Molecules

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“…It has previously been reported that some proteins, including proliferating cell nuclear antigen (PCNA), Oct4 and hypoxia-inducible factor-1α (HIF-1α), which maintain stemness of cancer stem cells, are regulated by the small ubiquitin-like modifier (SUMO) pathway ( 19 - 25 ). Due to the extensive and important role of SUMOs, direct SUMO gene silencing often leads to the death of various cell types, particularly precursor cells that participate in tissue repair, which may lead to serious side effects ( 26 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of SENP1 reduces the stemness capacity of osteosarcoma stem cells and increases their sensitivity to HSVtk/GCV

Liu

et al. 2018

Int J Oncol

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Osteosarcoma stem cells are able to escape treatment with conventional chemotherapeutic drugs, as the majority of them are in a quiescent state. Recent reports have suggested that small ubiquitin-like modifiers (SUMOs) serve important roles in the maintenance of cancer stem cell stemness. Therefore, a potential strategy to increase the effectiveness of chemotherapeutic agents is to interfere with SUMO modification of proteins associated with the maintenance of stemness in osteosarcoma stem cells. The present study revealed a significant decrease in the expression of SUMO1 specific peptidase 1 (SENP1) in osteosarcoma tissues and osteosarcoma cell lines, and SENP1 expression was much lower in osteosarcoma stem cells than in non-cancer stem cells. Further experiments indicated that the low levels of SENP1 were essential for maintenance of stemness in osteosarcoma stem cells. Overexpression of SENP1 resulted in a marked decrease in the maintenance of stemness, but only slightly induced apoptosis of osteosarcoma cells, which is crucial to reduce the side effects of drugs on normal precursor cells. Finally, SENP1 overexpression led to a significant increase in the sensitivity of osteosarcoma stem cells to the herpes simplex virus 1 thymidine kinase gene in combination with ganciclovir in vitro and in vivo. In conclusion, the present study described a novel method to increase the sensitivity of osteosarcoma stem cells to chemotherapeutic drugs. Notably, this approach may significantly reduce the required dose of conventional chemotherapeutic drugs and reduce side effects.

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Diarylurea derivatives comprising 2,4-diarylpyrimidines: Discovery of novel potential anticancer agents via combined failed-ligands repurposing and molecular hybridization approaches

Farag

Hassan

Chung

et al. 2020

Bioorganic Chemistry

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Arylurea Derivatives: A Class of Potential Cancer Targeting Agents

Cited by 8 publications

References 0 publications

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

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

Overexpression of SENP1 reduces the stemness capacity of osteosarcoma stem cells and increases their sensitivity to HSVtk/GCV

Diarylurea derivatives comprising 2,4-diarylpyrimidines: Discovery of novel potential anticancer agents via combined failed-ligands repurposing and molecular hybridization approaches

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