Discovery of N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives as potential antiproliferative agents by inhibiting MEK

Lv, Xian-Hai; Ren, Zi-Li; Zhou, Benguo; Liu, Qingshan; Chu, Ming-Jie; Liu, Dao-Hong; Mo, Kai; Zhang, Lisong; Yao, Xiaokang; Cao, Haiqun

doi:10.1016/j.bmc.2016.08.002

Cited by 24 publications

(14 citation statements)

References 34 publications

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“…N -(Benzyloxy)-1,3-diphenyl-1 H -pyrazole-4-carboxamide derivatives were synthesized and evaluated for anticancer activity as MEK inhibitors. Among these compounds, compound 285 showed the most potent inhibitory activity with IC 50 of 91 nM for MEK1 and GI 50 value of 0.26 μM for A549 cells [ 190 ].…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

et al. 2018

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Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.

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Section: Pharmacological Activitiesmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

et al. 2018

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“…In recent years, a number of key signalling pathways, membrane receptors, kinases, transcriptional factors, and other biological macromolecules have been identified, which results in further understanding on the pathogenesis of cancer 3 . Development of small molecular drugs specially targeting the key proteins in the signalling pathways relevant to tumourigenesis and tumour growth may provide opportunities to find new targeted anticancer agents with significantly improved therapeutic index.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and anticancer evaluation of novel quinoline derivatives of ursolic acid with hydrazide, oxadiazole, and thiadiazole moieties as potent MEK inhibitors

Jin

Chen

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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In this article, a series of novel quinoline derivatives of ursolic acid (UA) bearing hydrazide, oxadiazole, or thiadiazole moieties were designed, synthesised, and screened for their in vitro antiproliferative activities against three cancer cell lines (MDA-MB-231, HeLa, and SMMC-7721). A number of compounds showed significant activity against at least one cell line. Among them, compound 4d exhibited the most potent activity against three cancer cell lines with IC 50 values of 0.12 ± 0.01, 0.08 ± 0.01, and 0.34 ± 0.03 lM, respectively. In particular, compound 4d could induce the apoptosis of HeLa cells, arrest cell cycle at the G0/G1 phase, elevate intracellular reactive oxygen species level, and decrease mitochondrial membrane potential. In addition, compound 4d could significantly inhibit MEK1 kinase activity and impede Ras/Raf/ MEK/ERK transduction pathway. Therefore, compound 4d may be a potential anticancer agent and a promising lead worthy of further investigation.

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“…Chem. (2019) 11 (24) future science group type of fingerprint: C represents extended-connectivity fingerprints and P represents path-based fingerprints. These fingerprints are widely used for the prediction of other absorption, distribution, metabolism and excretion (ADME), quantitative structure-activity relationship (QSAR) and quantitative structure-property relationships (QSPR) [16][17][18].…”

Section: Classifier Model and P38α Mapk Inhibitor-like Library Constructionmentioning

confidence: 99%

“…Chem. (2019) 11 (24), 3125-3137 ISSN 1756-8919 3125 10.4155/fmc-2019-0223 C 2019 Newlands Press methods have successfully identified novel agents to perturb and combat kinase function, besides providing a number of small molecules for cancer therapy [11]. Herein, we selected two databases of small molecules which contain more than 3 million compounds in total and screened them in multiple models to construct a P38α inhibitor-like library.…”

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confidence: 99%

Discovering Novel P38α Inhibitors for the Treatment of Prostate Cancer Through Virtual Screening Methods

Tao

et al. 2019

Future Med. Chem.

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Aim: P38α plays a crucial role in the development of castration-resistant prostate cancer. Discovering novel inhibitors of P38α offers potential for the development of new anticancer drugs. Methods & results: Compounds from the Chemdiv and Enamine virtual libraries were filtered to construct the P38α inhibitor-like library. A total of 58 new P38α inhibitors were discovered via virtual screening; these included three compounds (compound 1, 5, 9) with kinase IC50 of below 10 μM. In vitro, these three compounds have the potential to suppress the viabilities of prostate cancer cell lines, however, only compound 9 can inhibit the proliferation and migration of prostate cancer cells. Conclusion: The potent compounds discovered in this study demonstrate anticancer functions by targeting the P38α mitogen-activated protein kinases signaling pathway and are worthy of further investigation.

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Discovery of N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives as potential antiproliferative agents by inhibiting MEK

Cited by 24 publications

References 34 publications

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Design, synthesis, and anticancer evaluation of novel quinoline derivatives of ursolic acid with hydrazide, oxadiazole, and thiadiazole moieties as potent MEK inhibitors

Discovering Novel P38α Inhibitors for the Treatment of Prostate Cancer Through Virtual Screening Methods

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