Synthesis and biological evaluation of N-aryl salicylamides with a hydroxamic acid moiety at 5-position as novel HDAC–EGFR dual inhibitors

Zuo, Miao; Zheng, Yu; Lu, Shemin; Li, Yan; Zhang, San‐Qi

doi:10.1016/j.bmc.2012.05.034

Cited by 39 publications

(25 citation statements)

References 30 publications

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“…Several studies were published, in which a series of newly-prepared salicylanilides showed antiproliferative activity against a spectrum of human cancer cell lines, such as promyelocytic leukaemia cells HL-60, chronic myelogenous leukaemia cells K562, human epithelial carcinoma cells A431, or breast carcinoma cells MCF-7. In addition, some salicylanilides have been recently reported to elicit cell cycle arrest or to induce apoptosis in human cancer cell lines [13,16,17,18]. …”

Section: Introductionmentioning

confidence: 99%

Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines

Kauerova

Kos

Goněc

et al. 2016

IJMS

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Ring-substituted hydroxynaphthanilides are considered as cyclic analogues of salicylanilides, compounds possessing a wide range of pharmacological activities, including promising anticancer properties. The aim of this study was to evaluate the potential anticancer effect of novel nitro-substituted hydroxynaphthanilides with a special focus on structure-activity relationships. The antiproliferative effect was assessed by Water Soluble Tetrazolium Salts-1 (WST-1) assay, and cytotoxicity was evaluated via dye exclusion test. Flow cytometry was used for cell cycle analysis and detection of apoptosis using Annexin V-FITC/PI assay. Protein expression was estimated by Western blotting. Our data indicate that the potential to cause the antiproliferative effect increases with the shift of the nitro substituent from the ortho- to the para-position. The most potent compounds, 3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide (2), and 2-hydroxy-N-(4-nitrophenyl)-naphthalene-1-carboxamide (6) showed antiproliferative activity against THP-1 and MCF-7 cancer cells without affecting the proliferation of 3T3-L1 non-tumour cells. Compounds 2 and 6 induced the accumulation of THP-1 and MCF-7 cells in G1 phase associated with the downregulation of cyclin E1 protein levels, while the levels of cyclin B1 were not affected. Moreover, compound 2 was found to exert the pro-apoptotic effect on the THP-1 cells. These results suggest that hydroxynaphthanilides might represent a potential model structure for the development of novel anticancer agents.

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Section: Introductionmentioning

confidence: 99%

Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines

Kauerova

Kos

Goněc

et al. 2016

IJMS

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“…Histone deacetylases inhibitors have also been shown to synergize with other anticancer agents to suppress proliferation and induce apoptosis in tumor cells (Erlich et al, 2012;Zuo et al, 2012;Cai et al, 2010;Chen et al, 2010). The phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in cancer cell initiation, growth, proliferation, and survival (Ciraolo et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

1,3,5-Triazine inhibitors of histone deacetylases: synthesis and biological activity

et al. 2014

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A series of 1,3,5-triazine-based hydroximic acids 6a-6i were designed and synthesized, and they were found to be potent inhibitors of human histone deacetylases. These compounds were evaluated for their antiproliferative activity by MTT assay, and most of them exhibited significant antiproliferative effect on HCT-116, MCF-7, and HeLa cancer cell lines. DNA flow cytometric analysis revealed that compound 6i induced apoptosis and cell cycle arrest at G2/M phase in HCT-116 cells.

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“…Using our established system, we screened several series of compounds, including compounds labelled W (N-(prop-2-ynyl)-4-(substituted phenylcarbonylamino) benzamides) [21], compounds labelled K (2-arylisoquinoline-1, 3(2H, 4H)-diones [22], compounds labelled Z (N-aryl salicylamides) [23], compounds labelled X (diaryl urea) [24], and compounds labelled S (5-(2-aminobenzo[d] hiazole-6-yl)-2-methoxy-3-(phenylsulfonylamino) benzamides) [25]. …”

Section: Methodsmentioning

confidence: 99%

Identification and application of anti-inflammatory compounds screening system based on RAW264.7 cells stably expressing NF-κB-dependent SEAP reporter gene

Ren

Lan

et al. 2017

BMC Pharmacol Toxicol

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BackgroundNF-κB is one of the key transcription factors in the inflammatory response, transactivates a series of pro-inflammatory genes and is therefore regarded as an important target for anti-inflammatory drug screening.MethodWe recombined the reporter gene vector with inserting the “neo” transcript into the vector pNF-κB-SEAP, made the reporter gene vector stable in a eukaryotic cell line. The recombinant reporter gene vector we named pNF-κB-SEAP-Neo was transfected into RAW264.7. We selected the transfected RAW264.7 cell line with G418 for 15 days and then get RAW264.7 cells stably expressing NF-κB-dependent SEAP named as RAW264.7-pNF-κB-SEAP cells. We treated the RAW264.7-pNF-κB-SEAP cells with NF-κB agonists as LPS, PolyI:C and TNF-α, NF-κB inhibitor as PDTC and BAY117085, in different concentrations and time points and tested the expression of the SEAP, constructed the drug screening system on the base of the RAW264.7-pNF-κB-SEAP cell line. 130 chemicals were screened with the drug screening system we constructed and one of these chemicals numbered w10 was found could inhibit the NF-κB significantly. At last, we verified the inhibition of w10 to expression of genes promoted with NF-κB in HepG2 and Hela, and to migration of Hela.ResultIn this study, we established a drug screening system based on RAW264.7 cells that stably expressed the NF-κB-dependent, SEAP reporter gene. To develop a standard method for drug screening using this reporter-gene cell line, the test approach of SEAP was optimized and basic conditions for drug screening were chosen. This included the initial cell number inoculated in a 96-well plate, the optimum agonist, inhibitor of NF-κB pathway and their concentrations during screening. Subsequently, 130 newly synthesized compounds were screened using the stable reporter-gene cell line. The anti-inflammatory effects of the candidate compounds obtained were further verified in 2 cancer cell lines. The results indicated that compound W10 (methyl 4-(4-(prop-2-yn-1-ylcarbamoyl) phenylcarbamoyl) benzoate) significantly inhibited SEAP production under the screening conditions. Further results confirmed that the precursor compound significantly inhibited the transcription of NF-κB target genes.ConclusionIn conclusion, RAW264.7 cells, stably expressing the NF-κB-dependent SEAP-reporter gene, may provide a new, feasible, and efficient cellular drug-screening system.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-016-0113-6) contains supplementary material, which is available to authorized users.

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Synthesis and biological evaluation of N-aryl salicylamides with a hydroxamic acid moiety at 5-position as novel HDAC–EGFR dual inhibitors

Cited by 39 publications

References 30 publications

Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines

Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines

1,3,5-Triazine inhibitors of histone deacetylases: synthesis and biological activity

Identification and application of anti-inflammatory compounds screening system based on RAW264.7 cells stably expressing NF-κB-dependent SEAP reporter gene

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