Ring-substituted 8-hydroxyquinoline-2-carboxanilides as potential antimycobacterial agents

Kos, Jiří; Zadražilová, Iveta; Nevin, Eoghan; Šoral, Michal; Goněc, Tomáš; Kollár, Péter; Oravec, Michal; Coffey, Aidan; O’Mahony, Jim; Liptaj, Tibor; Kráľová, Katarína; Jampílek, Josef

doi:10.1016/j.bmc.2015.06.047

Cited by 34 publications

(29 citation statements)

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“…The discussed 8‐hydroxyquinoline‐2‐carboxanilides were prepared via microwave‐assisted synthesis in high yields in short reaction time based on the recently published study . The condensation of activated 8‐hydroxyquinoline‐2‐carboxylic acid by phosphorus trichloride with ring‐substituted aniline in chlorobenzene gave a series of target compounds 1–32 , see Scheme .…”

Section: Resultsmentioning

confidence: 99%

“…[a] calculated using ACD/Percepta ver. 2012 (Advanced Chemistry Development, Toronto, ON, Canada); [b] published in Kos et al …”

Section: Resultsmentioning

confidence: 99%

“…At first, monosubstituted 8‐hydroxyquinoline‐2‐carboxanilides 1–22 , described recently by Kos et al., were evaluated against H5N1 influenza virus. Anti‐influenza activity was expressed as % of growth inhibition (GI) of H5N1 virus cultivated in the adenocarcinomic human alveolar basal epithelial cells (A549) at concentration 20 μg/mL.…”

Section: Resultsmentioning

confidence: 99%

“…This study is a follow‐up contribution to previously published papers,,, investigating a compound library comprising 8‐hydroxyquinolinecarboxanilides to counteract the deadly H5N1 virus. Based on the results of the primary screening of a mono‐substituted anilides as an original series, it was completed by specifically designed new di‐ and tri‐substituted anilides, and the structure–activity relationships (SAR) of all the mentioned compounds have been investigated.…”

Section: Introductionmentioning

confidence: 91%

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8‐Hydroxyquinoline‐2‐Carboxanilides as Antiviral Agents Against Avian Influenza Virus

Kos

Kapustíková

et al. 2019

ChemistrySelect

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Series of thirty‐two mono‐, di‐ and tri‐substituted 8‐hydroxyquinoline‐2‐carboxanilides were prepared by microwave‐assisted synthesis. The compounds were characterized, and their lipophilicity was experimentally determined. Primary in vitro screening of the cytotoxicity of all the synthesized compounds was performed using adenocarcinomic human alveolar basal epithelial cells (A549), and determined nontoxic compounds were then tested for their activity against highly pathogenic H5N1 avian influenza virus. 8‐Hydroxy‐N‐(3,4,5‐trichlorophenyl)quinoline‐2‐carboxamide, N‐(3‐chloro‐2‐fluorophenyl)‐8‐hydroxyquinoline‐2‐carboxamide and N‐(3,4‐dichlorophenyl)‐8‐hydroxyquinoline‐2‐carboxamide demonstrated the highest activity within the investigated series (IC50 = 11.3, 21.2 and 31.2 μM, respectively), while N‐(4‐chloro‐2‐fluorophenyl)‐8‐hydroxyquinoline‐2‐carboxamide expressed the highest cytotoxic effect (CC50 = 31.6 μM). In general, the inhibitory activity of the compounds depends on the position of halogen substituents on the anilide ring and is also affected by the lipophilicity and electron properties of individual substituents of the anilide part of the molecule. The structure‐activity relationships are discussed.

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Section: Resultsmentioning

confidence: 99%

“…[a] calculated using ACD/Percepta ver. 2012 (Advanced Chemistry Development, Toronto, ON, Canada); [b] published in Kos et al …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

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8‐Hydroxyquinoline‐2‐Carboxanilides as Antiviral Agents Against Avian Influenza Virus

Kos

Kapustíková

et al. 2019

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“…Similar effects were observed previously, for example, with ring-substituted 6-hydroxynaphthalene-2-carboxanilides, where 3-Cl, 4-Cl, 3-Br, and 3-CF 3 substituted derivatives decreased the viability of M. tuberculosis H37Ra in the range from 41.2% to 46.5% at the lowest tested concentration (MICs = 8 µg/mL) [20], with 8-hydroxy- N -(3-trifluoromethylphenyl)quinoline-2-carbox-amide, where the decrease of the viability of M. tuberculosis H37Ra was to 18.8% at MIC = 8 µg/mL [60], and with N -alkoxyphenylhydroxynaphthalenecarboxanilides substituted in C (3) ’ position of the anilide core by a longer alkoxy tail [61,62]. Since the MTT assay was positive, it can be stated that the tested compounds caused a decrease of mycobacterial cell metabolism.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides

Pospíšilová

Kos

Michnová

et al. 2018

IJMS

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A series of sixteen ring-substituted N-arylcinnamamides was prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra, Fusarium avenaceum, and Bipolaris sorokiniana. Several of the tested compounds showed antistaphylococcal, antitubercular, and antifungal activities comparable with or higher than those of ampicillin, isoniazid, and benomyl. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-phenylprop-2-enamide and (2E)-3-phenyl-N-[3-(trifluoromethyl)phenyl]prop-2-enamide showed the highest activities (MICs = 22.27 and 27.47 µM, respectively) against all four staphylococcal strains and against M. tuberculosis. These compounds showed an activity against biofilm formation of S. aureus ATCC 29213 in concentrations close to MICs and an ability to increase the activity of clinically used antibiotics with different mechanisms of action (vancomycin, ciprofloxacin, and tetracycline). In time-kill studies, a decrease of CFU/mL of >99% after 8 h from the beginning of incubation was observed. (2E)-N-(3,5-Dichlorophenyl)- and (2E)-N-(3,4-dichlorophenyl)-3-phenylprop-2-enamide had a MIC = 27.38 µM against M. tuberculosis, while a significant decrease (22.65%) of mycobacterial cell metabolism determined by the MTT assay was observed for the 3,5-dichlorophenyl derivative. (2E)-N-(3-Fluorophenyl)- and (2E)-N-(3-methylphenyl)-3-phenylprop-2-enamide exhibited MICs = 16.58 and 33.71 µM, respectively, against B. sorokiniana. The screening of the cytotoxicity of the most effective antimicrobial compounds was performed using THP-1 cells, and these chosen compounds did not shown any significant lethal effect. The compounds were also evaluated for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. (2E)-N-(3,5-dichlorophenyl)-3-phenylprop-2-enamide (IC50 = 5.1 µM) was the most active PET inhibitor. Compounds with fungicide potency did not show any in vivo toxicity against Nicotiana tabacum var. Samsun. The structure–activity relationships are discussed.

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8‐Hydroxyquinolines are bactericidal against Mycobacterium tuberculosis

Odingo

Early

Smith

et al. 2019

Drug Development Research

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There is an urgent need for new treatments effective against Mycobacterium tuberculosis, the causative agent of tuberculosis. The 8‐hydroxyquinoline series is a privileged scaffold with anticancer, antifungal, and antibacterial activities. We conducted a structure–activity relationship study of the series regarding its antitubercular activity using 26 analogs. The 8‐hydroxyquinolines showed good activity against M. tuberculosis, with minimum inhibitory concentrations (MIC90) of <5 μM for some analogs. Small substitutions at C5 resulted in the most potent activity. Substitutions at C2 generally decreased potency, although a sub‐family of 2‐styryl‐substituted analogs retained activity. Representative compounds demonstrated bactericidal activity against replicating M. tuberculosis with >4 log kill at 10× MIC over 14 days. The majority of the compounds demonstrated cytotoxicity (IC50 of <100 μM). Further development of this series as antitubercular agents should address the cytotoxicity liability. However, the 8‐hydroxyquinoline series represents a useful tool for chemical genomics to identify novel targets in M. tuberculosis.

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Ring-substituted 8-hydroxyquinoline-2-carboxanilides as potential antimycobacterial agents

Cited by 34 publications

References 46 publications

8‐Hydroxyquinoline‐2‐Carboxanilides as Antiviral Agents Against Avian Influenza Virus

8‐Hydroxyquinoline‐2‐Carboxanilides as Antiviral Agents Against Avian Influenza Virus

Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides

8‐Hydroxyquinolines are bactericidal against Mycobacterium tuberculosis

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