Acryloylamino-salicylanilides as EGFR PTK inhibitors

Deng, Wei; Guo, Zengjun; Guo, Yuchen; Feng, Zhiqiang; Yi, Jun; Chu, Frances

doi:10.1016/j.bmcl.2005.06.088

Cited by 36 publications

(18 citation statements)

References 20 publications

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“…Besides, it can be noted that the OH on the salicylic skeleton actually increased the inhibitory activity, comparing 17 to 27 . The deduction that the pseudo six-membered ring formed [25] through the intramolecular hydrogen bond between OH and O = C in the salicylic acid probably account for this issue above. The last one worth mentioning was that 22 with the methyl substituent is superior to 23 with the Cl atom and compounds with substitutions at the meta ( 18–20, 25 ) position showed less potent activities than those with substitutions at the para position ( 17 , 21 , 23 , 24 ).…”

Section: Resultsmentioning

confidence: 99%

Optimization of Substituted 6-Salicyl-4-Anilinoquinazoline Derivatives as Dual EGFR/HER2 Tyrosine Kinase Inhibitors

Qin

Sun

et al. 2013

PLoS ONE

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4-Anilinoquinazolines as an important class of protein kinase inhibitor are widely investigated for epidermal growth factor receptor (EGFR) tyrosine kinase or epidermal growth factor receptor 2 (HER2) inhibition. A series of novel 6-salicyl-4-anilinoquinazoline derivatives 9–27 were prepared and evaluated for their EGFR/HER2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on three variant cancer cell lines (A431, MCF-7, and A549). The bioassay results showed most of the designed compounds exhibited moderate to potent in vitro inhibitory activity in the enzymatic and cellular assays, of which compound 21 revealed the most potent dual EGFR/HER2 inhibitory activity, with IC50 values of 0.12 µM and 0.096 µM, respectively, comparable to the control compounds Erlotinib and Lapatinib. Furthermore, the kinase selectivity profile of 21 was accessed and demonstrated its good selectivity over the majority of the close kinase targets. Docking simulation was performed to position compound 21 into the EGFR/HER2 active site to determine the probable binding pose. These new findings along with molecular docking observations could provide an important basis for further development of compound 21 as a potent EGFR/HER2 dual kinase inhibitor.

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Section: Resultsmentioning

confidence: 99%

Optimization of Substituted 6-Salicyl-4-Anilinoquinazoline Derivatives as Dual EGFR/HER2 Tyrosine Kinase Inhibitors

Qin

Sun

et al. 2013

PLoS ONE

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“…On the molecular level, niclosamide inhibited multiple key oncogenic signalling pathways (e.g., Wnt/β-catenin, mTORC1, and NF-κB) [9,10,11,12]. In general, salicylanilide derivatives are presumed to share the structure similarity with the pharmacophore of 4-arylaminoquinazoline derivatives (e.g., gefitinib and erlotinib) that belong to the class of small molecule inhibitors of the protein kinase epidermal growth factor receptor (EGFR PTK) [13,14,15]. This fact led to the intensive research of salicylanilides anticancer properties, as their structure became an attractive model for the design of potent antitumor agents.…”

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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“…As shown in Scheme 1: i) substituted salicylic acid and an appropriate aniline are mixed in the presence of phosphorus trichloride [26,27] or thionyl chloride [28,29], and refluxed in chlorobenzene or toluene. Of course, "one-pot synthesis" are preferred.…”

Section: Synthesis Of Salicylanilidesmentioning

confidence: 99%

Salicylanilides and Their Derivates as Perspective Anti-tuberculosis Drugs: Synthetic Routes and Biological Evaluations

Imramovský

Pauk²,

Pejchal³

et al. 2011

MROC

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Salicylanilides are a well-known family of pharmacological compounds, which are under renewed investigation because of the discovery of novel interesting biological activities and mechanisms of action over the last decade. This comprehensive mini-review describes the biological and pharmacological properties of salicylanilides, their activity against atypical and multi-drug resistant mycobacterial strains, and synthetic routes for their preparation. In particular, this review focuses on the synthesis and biological properties of salicylanilides and O-substituted derivates reported between 2000 and 2010, which have displayed the highest antituberculosis or antifungal activity.

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Acryloylamino-salicylanilides as EGFR PTK inhibitors

Cited by 36 publications

References 20 publications

Optimization of Substituted 6-Salicyl-4-Anilinoquinazoline Derivatives as Dual EGFR/HER2 Tyrosine Kinase Inhibitors

Optimization of Substituted 6-Salicyl-4-Anilinoquinazoline Derivatives as Dual EGFR/HER2 Tyrosine Kinase Inhibitors

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

Salicylanilides and Their Derivates as Perspective Anti-tuberculosis Drugs: Synthetic Routes and Biological Evaluations

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