Design, synthesis and evaluation of anticancer activity of novel 2-thioxoimidazolidin-4-one derivatives bearing pyrazole, triazole and benzoxazole moieties

Elhady, Heba A.; El‐Sayed, Refat; Al-nathali, Hamedah S.

doi:10.1186/s13065-018-0418-1

Cited by 23 publications

(12 citation statements)

References 34 publications

(24 reference statements)

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“…We revealed a cytotoxic and apoptotic effect of compound 4 on a HepG2 cell line. Our results are consistent with a previous study [ 24 ], in which cytotoxicity of some 2-thioxoimidazolidin-4-one derivatives were studied against HepG2 cancer cell line with promising IC 50 values. As a result, apoptosis stimulation is regarded as a critical cellular event that contributes to the therapeutic effectiveness of anti-cancer drugs.…”

Section: Discussionsupporting

confidence: 93%

Evaluation of 2-Thioxoimadazolidin-4-one Derivatives as Potent Anti-Cancer Agents through Apoptosis Induction and Antioxidant Activation: In Vitro and In Vivo Approaches

et al. 2021

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Background: Hepatocellular carcinoma (HCC) is one of the most widespread malignancies and is reported as the fourth most prevalent cause of cancer deaths worldwide. Therefore, we aimed to investigate the probable mechanistic cytotoxic effect of the promising 2-thioxoimidazolidin-4-one derivative on liver cancer cells using in vitro and in vivo approaches. The compounds were tested for the in vitro cytotoxic activity using MTT assay, and the promising compound was tested in colony forming unit assay, flow cytometric analysis, RT-PCR, Western blotting, in vivo using SEC-carcinoma and in silico to highlight the virtual mechanism of action. Both compounds 4 and 2 performed cytotoxic effects against HepG2 cells with IC50 values of 0.017 and 0.18 μM, respectively, compared to Staurosporine and 5-Fu as reference drugs with IC50 values of 5.07 and 5.18 µM, respectively. Compound 4 treatment revealed apoptosis induction by 19.35-fold (11.42% compared to 0.59% in control), arresting the cell cycle at G2/M phase. Moreover, studying gene expression that plays critical roles in cell cycle and apoptosis by RT-PCR demonstrated that compound 4 enhances the expression of the pro-apoptotic genes p53, PUMA, and Caspase 3, 8, and 9, and impedes the anti-apoptotic Bcl-2 gene in the HepG2 cells. It can also inhibit the PI3K/AKT pathway at both gene and protein levels, which was reinforced by the in silico predictions of the molecular docking simulations towards the PI3K/AKT proteins. Finally, in vivo study verified that compound 4 has a promising anti-cancer activity through activating antioxidant levels (CAT, SOD and GSH) and ameliorating hematological, biochemical, and histopathological findings.

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Section: Discussionsupporting

confidence: 93%

Evaluation of 2-Thioxoimadazolidin-4-one Derivatives as Potent Anti-Cancer Agents through Apoptosis Induction and Antioxidant Activation: In Vitro and In Vivo Approaches

et al. 2021

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“…The two signals of the aromatic ring protons showed a doublet in the region of 7.86-7.84 ppm and a multiplet at 7.64-7.03 ppm. The presence of all carbon atoms for compounds 7e-h was con rmed by 13…”

Section: Resultsmentioning

confidence: 90%

“…Authors gratefully thank Central instrument laboratory, University of Tehran for performing 1 H-and 13 C-NMR, FT-IR, mass spectra, and owcytometry experiments analysis. Authors are also grateful to Dr. Ali…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…In the preparation of biologically active compounds, heterocyclic moieties or functions in the skeleton of 2-thioxoimidazolidine-4-one or thiohydantoin are widely used [9][10][11]. The studies revealed that 2-thioxo-4-imidazolidinone has anti-cancer activity and that these groups may be used to discover new anticancer agents [12,13]. In our study, we examined the function of new 2-thioxo-4-imidazolidinone derivatives against liver and cancer cells using the MTT assay, morphology changes, cell cycle, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Anti-Liver and Anti-Breast Cancer Activities of Novel 2-Thioxo-4-Imidazolidinone Derivatives

AbdulJabar

Al-Shawi

Mutlaq

2021

Preprint

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MTT assay and flowcytometry analysis were used to examine the anti-liver (HepG2) and anti-breast cancer (MCF-7) activities of twelve compounds derived from 2-thioxo-4-imidazolidine. The compounds 5a-h and 7f demonstrated significant anticancer activity against breast cancer cells, while the compounds 5a, ab, and 5d-h demonstrated significant anticancer activity against liver cancer cells, with varying IC50 values as compared to Cisplatin as the positive control. Among these compounds, we chose 5a, 5d, and 5h to detect cell cycle phases and late apoptosis. Compound 5a arrested MCF-7 cells in the S phase, while compound 5d arrested cells in the G1 phase. Compound 5a arrested S phase HepG2 cells, compound 5d arrested S phase cells, and compound 5h arrested G2 phase HepG2 cells. Compound 5a had a higher ratio of late apoptosis than compounds 5d and 5h on both cancer cells. Finally, the development of these compounds as new anti-breast and anti-liver agents warrants further research to understand the mechanism of action, especially against breast cancer.

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“…Fused pyrazole derivatives showed anticancer activity on human breast cancer (MCF-7) cell lines. [18] Elhady et al, [19] reported the anticancer activity of 2-thioxoimidazolidin-4-one derivatives bearing pyrazole, triazole, and benzoxazole moieties on hepatocellular carcinoma (HepG2) and breast carcinoma (MCF-7) cell lines. Quinolineimidazole derivatives showed antitumor activity on A549 and MCF-7 cell lines with better activity when a bromine atom replaced the C-6 of the quinoline ring.…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

Synthesis, Characterization, and Anticancer Studies of Some Pyrazole‐Based Hybrid Heteroatomics

Kuthyala

Sheik²,

Prabhu

et al. 2020

ChemistrySelect

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Defined with a dual‐mode of action, the hybrid molecule synthesis is an attractive strategy to endure the scientific challenges in drug discovery. Besides worthy development in cancer therapy, it is still a leading cause of death across the globe. Failure in terms of efficacy, selectivity and toxicity, the statistics of a potential drug to concrete the cancer is rather in bleak. In the present study, synthesized hybrid molecules were well characterized by spectroscopy techniques. The single‐crystal X‐ray crystallography study revealed the monoclinic crystal system of Dimethyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(3‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1H‐pyrazol‐4‐yl)pyridine‐3,5‐dicarboxylate (5 b) with spacegroup C2/c. MTT assay provided the anticancer property of the compounds Diethyl1,4‐dihydro‐3,5‐dimethyl‐4‐(3‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1H‐pyrazol‐4‐yl)pyridine‐2,6‐dicarboxylate (5 a) and 5‐methyl‐1‐phenyl‐4‐(4‐(4,5‐diphenyl‐1H‐imidazol‐2‐yl)‐1H‐pyrazol‐3‐yl)‐1H‐pyrazole (6 a) against A549 cell lines with the IC50 values of 42.79 μM and 55.13 μM respectively. The AO‐EB staining assay for cell death analysis confirmed the selective action of both 5 a and 6 a. Further, molecular docking confirmed the effective binding with cyclin‐dependent kinase (CDK2) protein, suggesting that the target compounds are remarkable inhibitors in dysregulating the CDK2 protein in cancer cells.

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Design, synthesis and evaluation of anticancer activity of novel 2-thioxoimidazolidin-4-one derivatives bearing pyrazole, triazole and benzoxazole moieties

Cited by 23 publications

References 34 publications

Evaluation of 2-Thioxoimadazolidin-4-one Derivatives as Potent Anti-Cancer Agents through Apoptosis Induction and Antioxidant Activation: In Vitro and In Vivo Approaches

Evaluation of 2-Thioxoimadazolidin-4-one Derivatives as Potent Anti-Cancer Agents through Apoptosis Induction and Antioxidant Activation: In Vitro and In Vivo Approaches

Anti-Liver and Anti-Breast Cancer Activities of Novel 2-Thioxo-4-Imidazolidinone Derivatives

Synthesis, Characterization, and Anticancer Studies of Some Pyrazole‐Based Hybrid Heteroatomics

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