Design and synthesis of novel 1-phenyl-3-(5-(pyrimidin-4-ylthio)-1,3,4-thiadiazol- 2-yl)urea derivatives with potent anti-CML activity throughout PI3K/AKT signaling pathway

Li, Weiwei; Chu, Jianjie; Fan, Tingting; Zhang, Wei; Ning, Zeqiong; Wang, Mingming; Sun, Jin; Zhao, Xian; Wen, Aidong

doi:10.1016/j.bmcl.2019.05.005

Cited by 11 publications

(9 citation statements)

References 21 publications

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“…By reacting 5-amino-1,3,4-thiadiazole-2-thiol (III) with different phenyl isocyanates under reflux for 5 hours while utilizing acetonitrile as a solvent, the main intermediates 5 were produced ( Scheme 2 ). 37 , 38 …”

Section: Resultsmentioning

confidence: 99%

Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents

Al‐Sanea

Hamdi

Brogi

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles ( 4a-d) , 1,3,4-thiadiazoles ( 6a - d) , and pyrimidines ( 8a - d) , was preparedand assessed for its potential in vitro COX-2 inhibitors. Compared to Celecoxib, compounds 4b-d and 8d were the most potent derivatives c with a half-maximal inhibitory concentration range of 53–69 nM. Considering COX-2 selectivity index, compounds 4 b and 4c were chosen among these most potent derivatives for further investigation. The in vivo ability of compounds 4 b and 4c to counteract carrageenan-induced paw edoema has been assessed and their potential underlying mechanisms have been elucidated and the results have been further validated using molecular docking simulations.

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Section: Resultsmentioning

confidence: 99%

Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents

Al‐Sanea

Hamdi

Brogi

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…The diarylurea 12 exhibited the least cytotoxicity and higher biological activity (IC 50 = 0.038 µM). It also displayed good induced-apoptosis effect for human CML cell line K562; its effect seems to happen via a significant reduction of protein phosphorylation of PI3K/AKT signal pathway by human phospho-kinase array analysis [112]. Forchlorfenuron (FCF; N-(2-Chloro-4-pyridyl)-N'-phenylurea) is a small synthetic diarylurea currently used in agriculture as a plant fertilizer that increases fruit size because of its potent cytokinin activity.…”

Section: Other Diarylureasmentioning

confidence: 99%

Diarylureas as Antitumor Agents

et al. 2021

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The diarylurea is a scaffold of great importance in medicinal chemistry as it is present in numerous heterocyclic compounds with antithrombotic, antimalarial, antibacterial, and anti-inflammatory properties. Some diarylureas, serine-threonine kinase or tyrosine kinase inhibitors, were recently reported in literature. The first to come into the market as an anticancer agent was sorafenib, followed by some others. In this review, we survey progress over the past 10 years in the development of new diarylureas as anticancer agents.

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“…On the other hand, urea derivatives are widely applied in medicinal synthesis due to their various biological activities, such as anti-inflammatory ( Drexel et al, 2019 ), antitumor activities ( Kang et al, 2019 ; Kilic-Kurta et al, 2020 ), and antimicrobial ( Lafzi et al, 2021 ). Recent reports showed that urea derivatives could inhibit cell signaling transduction, such as RAS-RAFMEK-ERK signaling pathway and PI3K/Akt/mTOR pathway ( Li et al, 2019 ), and inhibit protein activity, such as mTORC1 and mTORC2 ( Gao et al, 2018 ). Thus, to design new compounds with urea moiety to explore chemotherapy agents is a feasible strategy.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antitumor Evaluation of Menthone-Derived Pyrimidine-Urea Compounds as Potential PI3K/Akt/mTOR Signaling Pathway Inhibitor

et al. 2022

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A series of novel menthone derivatives bearing pyrimidine and urea moieties was designed and synthesized to explore more potent natural product-derived antitumor agents. The structures of the target compounds were confirmed by FTIR, NMR, and HRMS. The in vitro antitumor activity was tested by standard methyl thiazolytetrazolium assay and showed that 4i, 4g, 4s, and 4m are the best compounds with IC50 values of 6.04 ± 0.62µM, 3.21 ± 0.67µM, 19.09 ± 0.49µM, and 18.68 ± 1.53µM, against Hela, MGC-803, MCF-7, and A549, respectively. The results of the preliminary action mechanism studies showed that compound 4i, the representative compound, could induce cell apoptosis in Hela cells in a dose-dependent manner and might arrest the cell cycle in the G2/M phase. Furthermore, the results of network pharmacology prediction and Western blot experiments indicated that compound 4i might inhibit Hela cells through inhibit PI3K/Akt/mTOR signaling pathway. The binding modes and the binding sites interactions between compound 4i and the target proteins were predicted preliminarily by the molecular docking method.

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Design and synthesis of novel 1-phenyl-3-(5-(pyrimidin-4-ylthio)-1,3,4-thiadiazol- 2-yl)urea derivatives with potent anti-CML activity throughout PI3K/AKT signaling pathway

Cited by 11 publications

References 21 publications

Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents

Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents

Diarylureas as Antitumor Agents

Synthesis and Antitumor Evaluation of Menthone-Derived Pyrimidine-Urea Compounds as Potential PI3K/Akt/mTOR Signaling Pathway Inhibitor

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