1867-44-3Relevant articles and documents
Synthesis of new arylazopyrazoles as apoptosis inducers: Candidates to inhibit proliferation of MCF-7 cells
Ismail, Magda M. F.,Soliman, Dalia H.,Sabour, Rehab,Farrag, Amel M.
, (2021)
New 4-arylazo-3,5-diamino-1H-pyrazole derivatives substituted in the 4-aryl ring with the acetyl moiety were designed and synthesized. The antiproliferative activity of the novel arylazopyrazoles was examined against the MCF-7 cell line. Among all target compounds, 8b (IC50 3.0 μM) and 8f (IC50 4.0 μM) displayed higher cytotoxicity as compared with the reference standard imatinib (IC50 7.0 μM). Further studies to explore the mechanism of action were performed on the most active hit of our library, 8b, via anti-CDK2 kinase activity. It demonstrated good inhibitory effects for CDK2 (IC50 0.24 μM) with 62.5% inhibition, compared with imatinib. The cell cycle analysis in the MCF-7 cell line revealed apoptosis induction by 8b and cell cycle arrest at the S phase. Docking in the CDK2 active site and pharmacophore modeling confirmed the affinity of 8b to the CDK2 active site. Absorption, distribution, metabolism, and excretion studies revealed that our target compounds are orally bioavailable, with no permeation through the blood–brain barrier.
Synthesis, antitumor activity, pharmacophore modeling and qsar studies of novel pyrazoles and pyrazolo [1, 5-A] pyrimidines against breast adenocarcinoma MCF-7 cell line
Ismail, Magda M. F.,Soliman, Dalia H.,Farrag, Amel M.,Sabour, Rehab
, p. 434 - 442 (2016/07/12)
Objective: The present work aimed to synthesize New series of pyrazoles 3 and pyrazolo[1,5-a]pyrimidines 5, 7, 9 in order to evaluate their antiproliferative activity against human breast adenocarcinoma MCF-7cell line and study the cell cycle progression of the most active compounds. In addition, Pharmacophore modeling and QSAR Studies of these new compounds were done. Methods: The diazonium salt of 4-aminoacetophenone 1 was coupled with malononitrile in ethanol using sodium acetate affords 2-[(4-acetylphenyl)diazenyl] malononitrile Cycloaddition of hydrazine hydrate, in molar ratios 1:1 or 1:2, on compound 2, furnished 3,5-diaminopyrazolederivatives 3a and 3b respectively. Moreover, new pyrazolo[1,5-a]pyrimidine derivatives 5a-f were obtained upon cyclocondensation of 3a, b with different chalcones 4a-c in EtOH/piperidine,while compounds 7a-f were prepared via cycloaddition of 3a, b with various arylidene malononitriles 6a-c in the same reaction condition. Finally, treatment of 3a, b with ethyl 2-cyano-3-ethoxyacrylate 8a or 2-(ethoxymethylene)malononitrile 8b in EtOH/TEA yielded the novel pyrazolo[1,5-a]pyrimidine derivatives 9a, b respectively. These target compounds were screened for their cytotoxic activity against MCF-7 (human breast Cell Line) followed by study cell cycle of 7a. Finally, Pharmacophore modeling and QSAR Studies was carried out. Results: The pyrazolopyrimidine 7a was the most active compound (IC50 = 3.25 μM), whereas, some of the tested compounds exploited moderate growth inhibitory activity. Its effect was further studied on cell cycle progression; results showed that compound 7a induced cell cycle arrest at S-phase verifying this compound as a promising selective anticancer agent. Conclusion: Compound 7a was found to be the most active member against MCF-7 breast cancer (IC50= 3.25 μM), Further biological assessment of 7a using flow-cytometric analysis, revealed that it induced cell cycle arrest at S phase.
