EGFR/VEGFR-2 dual inhibitor and apoptotic inducer: Design, synthesis, anticancer activity and docking study of new 2-thioxoimidazolidin-4one derivatives

Mourad, Ahmed A.E.; Farouk, N.; El‐Sayed, Elsherbiny H.; Mahdy, Ahmed R.E.

doi:10.1016/j.lfs.2021.119531

Cited by 19 publications

(7 citation statements)

References 49 publications

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“… 11,25 It's interesting to note the emergence of the thiohydantoin ring as an efficient pharmacophoric ingredient in the development of potent inhibitors for EGFR and VEGFR growth factor receptors. 26,27 Many hybrid hydantoin/thiohydantoin-supported chemical entities have been approved as clinical medications. 11 …”

Section: Introductionmentioning

confidence: 99%

Novel imidazolium-thiohydantoin hybrids and their Mn(iii) complexes for antimicrobial and anti-liver cancer applications

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Novel imidazolium-thiohydantoin hybrids and their Mn(iii) complexes for antimicrobial and anti-liver cancer applications

et al. 2022

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“…In order to investigate the EGFR inhibition potential of the most active anticancer compound ( 7c ), an EFGR kinase assay kit (BPS Bioscience, San Diego, CA, USA) was used as per the manufacturer’s instructions and the protocol is reported [ 50 ]. The IC 50 values for the tested compound ( 7c ) and the reference drug (erlotinib) were determined in a molar concentration using the GraphPad prism 9 software.…”

Section: Resultsmentioning

confidence: 99%

“…The IC 50 values for the tested compound (7c) and the reference drug (erlotinib) were determined in a molar concentration using the GraphPad prism 9 software. The inhibition assays were performed in triplicate and their results showed that the compound displayed an inhibition of the EGFR with an IC 50 value of 42.91 ± 0.80 nM, while the standard drug erlotinib displayed an IC 50…”

Section: In Vitro Egfr Kinase Inhibition Assaymentioning

confidence: 99%

An Efficient Synthesis of 1-(1,3-Dioxoisoindolin-2-yl)-3-aryl Urea Analogs as Anticancer and Antioxidant Agents: An Insight into Experimental and In Silico Studies

Afzal,

Ahsan

2023

Molecules

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The present investigation reports the efficient multistep synthesis of 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) in good yields. All the 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) were characterized by spectroscopic techniques. Five among the six compounds were tested against 56 cancer cell lines at 10 µM as per the standard protocol. 1-(4-Bromophenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7c) exhibited moderate but significant anticancer activity against EKVX, CAKI-1, UACC-62, MCF7, LOX IMVI, and ACHN with percentage growth inhibitions (PGIs) of 75.46, 78.52, 80.81, 83.48, 84.52, and 89.61, respectively. Compound 7c was found to exhibit better anticancer activity than thalidomide against non-small cell lung, CNS, melanoma, renal, prostate, and breast cancer cell lines. It was also found to exhibit superior anticancer activity against melanoma cancer compared to imatinib. Among the tested compounds, the 4-bromosubstitution (7c) on the phenyl ring demonstrated good anticancer activity. Docking scores ranging from −6.363 to −7.565 kcal/mol were observed in the docking studies against the molecular target EGFR. The ligand 7c displayed an efficient binding against the EGFR with a docking score of −7.558 kcal/mol and displayed an H-bond interaction with Lys745 and the carbonyl functional group. Compound 7c demonstrated a moderate inhibition of EGFR with an IC50 of 42.91 ± 0.80 nM, in comparison to erlotinib (IC50 = 26.85 ± 0.72 nM), the standard drug. The antioxidant potential was also calculated for the compounds (7a–f), which exhibited good to low activity. 1-(2-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7f) and 1-(4-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7d) demonstrated significant antioxidant activity with IC50 values of 15.99 ± 0.10 and 16.05 ± 0.15 µM, respectively. The 2- and 4-methoxysubstitutions on the N-phenyl ring showed good antioxidant activity among the series of compounds (7a–f). An in silico ADMET prediction studies showed the compounds’ adherence to Lipinski’s rule of five: they were free from toxicities, including mutagenicity, cytotoxicity, and immunotoxicity, but not for hepatotoxicity. The toxicity prediction demonstrated LD50 values between 1000 and 5000 mg/Kg, putting the compounds either in class IV or class V toxicity classes. Our findings might create opportunities for more advancements in cancer therapeutics.

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“…The immunohistochemical results lend additional substantiation to the hypothesis of self-sufficiency for the sarcoma-induced lung tumors, having demonstrated a steady overexpression of critical tumor promotion pillars as: (1) a potent transforming and selfautonomy conferring growth factor as TGF-α [50], a prominent oncogene as c-Myc [51], a validated cell proliferation marker as PCNA [52], and two growth factors receptors involved in cancer cells proliferation, immortality, self-autonomy, metastasis, angiogenesis, and reprogramming as EGF-Receptor and VEGF-Receptor 2 [53]. These observations rise the question on what mechanism (s) may be underlying the overexpression of these markers and whether this is associated to an enhanced functional activity.…”

Section: Discussionmentioning

confidence: 99%

Induction of Premalignant and Malignant Changes in Nude Mice by Human Tumors-Derived Cell-Free Filtrates

Berlanga-Acosta¹,

Mendoza-Mari²,

Martinez-Jimenez³

et al. 2022

annhematoloncol

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Carcinogenesis is a vast and heterogeneous, multi-step process driven by genetic and epigenetic operators leading to superimposed “tumor organs”. Based on our previous experiences of reproducing human donor’s histopathological hallmarks in healthy animals exposed to pathologic tissues homogenates, we examined the consequences of administering crude homogenates elaborated from invasive human tumors to nude mice. Subcutaneous administrations of increasing protein concentrations of breast carcinoma homogenates for 6 and 12 weeks, induced lungs atypical adenomatous hyperplasia, foci of lepidic and solid growth poorly-differentiated adenocarcinomas at the two time points. Non-atypical mucosal hyperplasia and adenomas were detected along the gastrointestinal tract. Another experiment addressed the impact of daily administrations (100 μg protein/mouse) of anaplastic sarcoma tissue homogenate for a month. This scheme triggered proliferative changes including: lung adenocarcinomas; a subcutaneous, poorly-differentiated mesenchymal cells tumor, a lymphoadenoma, and multiple gastrointestinal adenomas. When 50% of the month-treated animals were left to evolve treatment-free for other 35 days, a larger and broader incidence of neoplastic changes was found, suggesting autonomous growth: lung adenocarcinomas, a poorly differentiated thyroid tumor, an epithelial tumor within the periaortic brown adipose tissue, and multiple adenomas. These findings indicate that tumor crude homogenates contains soluble “transforming” messengers, that in a short period of time disrupt tissues’ proliferative and differentiation programs drifting to progressive neoplasms. This study expands previous evidences on the ability of human pathologic tissues-derived homogenates, to induce the reproduction of diseased donor’s histopathologic hallmarks.

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EGFR/VEGFR-2 dual inhibitor and apoptotic inducer: Design, synthesis, anticancer activity and docking study of new 2-thioxoimidazolidin-4one derivatives

Cited by 19 publications

References 49 publications

Novel imidazolium-thiohydantoin hybrids and their Mn(iii) complexes for antimicrobial and anti-liver cancer applications

Novel imidazolium-thiohydantoin hybrids and their Mn(iii) complexes for antimicrobial and anti-liver cancer applications

An Efficient Synthesis of 1-(1,3-Dioxoisoindolin-2-yl)-3-aryl Urea Analogs as Anticancer and Antioxidant Agents: An Insight into Experimental and In Silico Studies

Induction of Premalignant and Malignant Changes in Nude Mice by Human Tumors-Derived Cell-Free Filtrates

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