Synthesis and antiproliferative activities against Hep-G2 of salicylanide derivatives: potent inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase

Zhu, Ziqi; Shi, Lei; Ruan, Xiao-Ming; Yang, Ying; Li, Huan‐Qiu; Xu, Suo-Ping; Zhu, Hai‐Liang

doi:10.3109/14756361003671060

Cited by 16 publications

(14 citation statements)

References 23 publications

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“…Out of 66 screened compounds seven showed promising inhibition properties at a concentration of 1 µm (>90% or >80% inhibition for MAO B and A, respectively). Evaluation of their IC 50…”

Section: Resultsmentioning

confidence: 99%

“…Monoamine oxidase A/B inhibition assays were performed as described previously using the discontinuous fluorimetric method with kynuramine as MAO substrate. 21 For the screening (test concentration: 10 −6 M) and IC 50 Figure S12 in supplemental material) or set to zero in case when the bottom plateau was not reached with highest concentration tested (leading to "IC 50 estimates").…”

Section: Enzymologymentioning

confidence: 99%

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<p>Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs</p>

Hagenow¹,

Hagenow²,

Grau³

et al. 2020

DDDT

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Background: Ligands consisting of two aryl moieties connected via a short spacer were shown to be potent inhibitors of monoamine oxidases (MAO) A and B, which are known as suitable targets in treatment of neurological diseases. Based on this general blueprint, we synthesized a series of 66 small aromatic amide derivatives as novel MAO A/B inhibitors. Methods: The compounds were synthesized, purified and structurally confirmed by spectroscopic methods. Fluorimetric enzymological assays were performed to determine MAO A/B inhibition properties. Mode and reversibility of inhibition was determined for the most potent MAO B inhibitor. Docking poses and pharmacophore models were generated to confirm the in vitro results. Results: N-(2,4-Dinitrophenyl)benzo[d][1,3]dioxole-5-carboxamide (55, ST-2043) was found to be a reversible competitive moderately selective MAO B inhibitor (IC 50 = 56 nM, K i = 6.3 nM), while N-(2,4-dinitrophenyl)benzamide (7, ST-2023) showed higher preference for MAO A (IC 50 = 126 nM). Computational analysis confirmed in vitro binding properties, where the anilides examined possessed high surface complementarity to MAO A/B active sites. Conclusion: The small molecule anilides with different substitution patterns were identified as potent MAO A/B inhibitors, which were active in nanomolar concentrations ranges. These small and easily accessible molecules are promising motifs, especially for newly designed multitargeted ligands taking advantage of these fragments.

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“…Out of 66 screened compounds seven showed promising inhibition properties at a concentration of 1 µm (>90% or >80% inhibition for MAO B and A, respectively). Evaluation of their IC 50…”

Section: Resultsmentioning

confidence: 99%

Section: Enzymologymentioning

confidence: 99%

<p>Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs</p>

Hagenow¹,

Hagenow²,

Grau³

et al. 2020

DDDT

View full text Add to dashboard Cite

show abstract

“…aureus but did not have any effect on bacterial or erythrocyte membranes. The authors of another study [ 64 ] tested the effects of 32 salicylanilide derivatives on HepG2 cells and observed varying degrees of toxicities. The findings from our study and earlier studies suggest that niclosamide and oxyclozanide may have more than one mechanism.…”

Section: Discussionmentioning

confidence: 99%

Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus

et al. 2015

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Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections.

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“…Salicylanilide scaffold represents still an investigated group of compounds with many interesting pharmacological properties. Recently, they have been reported, e.g., as potential agents with a significant activity against Onchocerca volvulus [ 15 ], Toxoplasma gondii parasite [ 16 ] or with anticancer features [ 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Activity of Salicylanilide 4-(Trifluoromethyl)-benzoates

et al. 2013

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The development of novel antimicrobial agents represents a timely research topic. Eighteen salicylanilide 4-(trifluoromethyl)benzoates were evaluated against Mycobacterium tuberculosis, M. avium and M. kansasii, eight bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) and for the inhibition of mycobacterial isocitrate lyase. Some compounds were further screened against drug-resistant M. tuberculosis and for their cytotoxicity. Minimum inhibitory concentrations (MICs) for all mycobacterial strains were within 0.5–32 μmol/L, with 4-chloro-2-[4-(trifluoromethyl)phenylcarbamoyl]phenyl 4-(trifluoromethyl)benzoate superiority. Gram-positive bacteria including MRSA were inhibited with MICs ≥ 0.49 μmol/L, while Gram-negative ones were much less susceptible. Salicylanilide 4-(trifluoromethyl)benzoates showed significant antibacterial properties, for many strains being comparable to standard drugs (isoniazid, benzylpenicillin) with no cross-resistance. All esters showed mild inhibition of mycobacterial isocitrate lyase and four compounds were comparable to 3-nitropropionic acid without a direct correlation between in vitro MICs and enzyme inhibition.

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Synthesis and antiproliferative activities against Hep-G2 of salicylanide derivatives: potent inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase

Cited by 16 publications

References 23 publications

<p>Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs</p>

<p>Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs</p>

Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus

Antibacterial Activity of Salicylanilide 4-(Trifluoromethyl)-benzoates

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