URD12: A urea derivative with marked antitumor activities

Wang, Aiyun; Lu, Yin; Zhu, Hai‐Liang; Jiao, Qingcai

doi:10.3892/ol.2011.474

Cited by 6 publications

(3 citation statements)

References 15 publications

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“…Urea-based compounds are largely present in nature and have received special attention due to their potent anticancer properties (Li, Lv, Yan, & Zhu, 2009). The urea derivatives, including alkyl ureas, arylureas, and thioureas, represent one of the most useful classes of anticancer agents, with a wide range of activities against various cancers (Wang, Lu, Zhu, & Jiao, 2012). Duan et al (2013) discovered that a number of 1,2,3-triazole-dithiocarbamate-urea hybrids displayed high activity against the proliferation of different human cancer cells in-vitro.…”

Section: Cytotoxicity Assessment Of Test Compounds Against In A549 Cellsmentioning

confidence: 99%

Design, synthesis, and characterization of α, β‐unsaturated carboxylic acid, and its urea based derivatives that explores novel epigenetic modulators in human non‐small cell lung cancer A549 cell line

Anusha

Sundararaju

Chidambaram³

et al. 2018

Journal Cellular Physiology

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Histone deacetylase inhibitors (HDACi) are a small molecule chemotherapeutics that target the chromatin remodeling through the regulation of histone and non-histone proteins. These inhibitors directed against histone deacetylase (HDAC) enzymes have become an important therapeutic tool in oncology; consequently, scientific efforts have fortified the quest for newer and novel HDACi, which forces the design of structurally innovative HDACi. Various urea containing compounds exhibited admirable anticancer activity. On the basis of these observations, we design and synthesize HDAC specific blocker molecules which are specifically besieged towards class I, class II, and class IV HDAC isoforms to enhance the structural assortment for HDACi. Through docking experiments, we identified that the compounds were tightly bound to the isoforms of the HDAC enzymes at their receptor regions. These derivatives potently inhibited the different isoforms, namely, class I, II, and IV of HDACs, by hyperacetylation of lysine residues in A549 cells. The mechanism of apoptosis is evident, regulating tumor suppressor genes and proteins, thereby facilitating the activation of the death receptor pathway by the tumor necrosis factor (TNF) receptor. These derivative facilitated the induction of reactive oxygen species (ROS) generation leading to downregulation of Bcl , and upregulation of Bax expression, thereby dysregulating mitochondrial membrane potential (ΔΨ ) to release cytochrome c, and activation of intrinsic pathway. These compounds downregulate the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway to inhibit cell growth, proliferation, and metastasis through the matrix metalloproteinases (MMPs) MMP2 and MMP9 in A549 cells. These results suggest that our designed urea based derivatives act as epigenetic targeting agents through HDAC inhibition.

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Section: Cytotoxicity Assessment Of Test Compounds Against In A549 Cellsmentioning

confidence: 99%

Design, synthesis, and characterization of α, β‐unsaturated carboxylic acid, and its urea based derivatives that explores novel epigenetic modulators in human non‐small cell lung cancer A549 cell line

Anusha

Sundararaju

Chidambaram³

et al. 2018

Journal Cellular Physiology

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“…On the other hand, the aryl-urea or sulfonyl-urea derivatives are of great interest in various areas of organic chemistry, coordination chemistry, and medicinal chemistry (Fig. 1 ) 9 – 16 . It was reported the anticancer activity of several urea derivatives including N -nitroso-urea which is an alkylating agent drug 17 , 18 .…”

Section: Introductionmentioning

confidence: 99%

Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies

Sroor,

Mahrous,

El-Kader

et al. 2023

Sci Rep

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We designed and prepared a novel series of urea derivatives with/without sulfonyl group in their structures to investigate the impact of the sulfonyl group on the biological activity of the evaluated compounds. Antibacterial investigations indicated that derivatives 7, 8, 9, and 11 had the most antibacterial property of all the compounds examined, their minimum inhibitory concentrations (MICs) determined against B. mycoides, E. coli, and C. albicans, with compound 8 being the most active at a MIC value of 4.88 µg/mL. Anti-cancer activity has been tested against eight human cancer cell lines; A549, HCT116, PC3, A431, HePG2, HOS, PACA2 and BJ1. Compounds 7, 8 and 9 emerged IC50 values better than Doxorubicin as a reference drug. Compounds 7 and 8 showed IC50 = 44.4 and 22.4 μM respectively against PACA2 compared to Doxorubicin (IC50 = 52.1 μM). Compound 9 showed IC50 = 17.8, 12.4, and 17.6 μM against HCT116, HePG2, and HOS, respectively. qRT-PCR revealed the down-regulation of PALB2 in compounds 7 and 15 treated PACA2 cells. Also, the down-regulation of BRCA1 and BRCA2 was shown in compound 7 treated PC3 cells. As regard A549 cells, compound 8 decreased the expression level of EGFR and KRAS genes. While compounds 7 and 9 down-regulated TP53 and FASN in HCT116 cells. Molecular docking was done against Escherichia coli enoyl reductase and human Son of sevenless homolog 1 (SOS1) and the results showed the promising inhibition of the studied proteins.

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“…Wang et al . [ 72 ] further studied URD12 in In vivo and in vitro assays using BGC-823 human gastric carcinoma, SMMC-7721 human hepatoma, and HepG2 human hepatocellular carcinoma cell lines [ Figure 2 ]. URD12 was confirmed to inhibit the growth of tested tumor cell lines with no effects on the weight, spleen, and thymus.…”

Section: Introductionmentioning

confidence: 99%

The biological roles of urea: A review of preclinical studies

et al. 2022

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Urea is an organic compound that has been reported to be effective against many pathological conditions. However, many other studies have reported the toxic effects of urea. These controversies on the biological roles of urea remain unresolved. This review aims to evaluate the biological roles of urea in experimental animals from data published in peer-reviewed journals. A PubMed search was conducted using the phrase, “urea application in experimental animals.” A total of 13 publications that met the inclusion criteria were evaluated. The test substance, animal model, number of animals, doses, duration of treatment, and effects were recorded. Regarding the toxic effect, urea caused decreased excretion of other nitrogenous compounds, increased oxidative stress, decreased insulin, and impairment of beta-cell glycolysis. Furthermore, it caused endothelial dysfunction, loss of synapsis, and decreased olfaction. Regarding the therapeutic effects, urea caused increased growth, increased digestion, and decreased hepatic dysfunction. It also induced apoptosis of tumor cells and exerted neuroprotective properties. Products containing urea should be used with caution, especially in individuals with symptoms of chronic kidney disease. However, more studies are needed to elucidate the mechanisms of its therapeutic effects.

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URD12: A urea derivative with marked antitumor activities

Cited by 6 publications

References 15 publications

Design, synthesis, and characterization of α, β‐unsaturated carboxylic acid, and its urea based derivatives that explores novel epigenetic modulators in human non‐small cell lung cancer A549 cell line

Design, synthesis, and characterization of α, β‐unsaturated carboxylic acid, and its urea based derivatives that explores novel epigenetic modulators in human non‐small cell lung cancer A549 cell line

Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies

The biological roles of urea: A review of preclinical studies

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