Synthesis and spectrum of biological activities of novel N-arylcinnamamides

Sarka Pospisilova, Jiri Kos, Hana Michnova, Iva Kapustikova, Tomas Strharsky, Michal Oravec, A. Móricz, Jozsef Bakonyi, Tereza Kauerova, Peter Kollar, Alois Cizek, Josef Jampilek

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number2318
JournalInternational Journal of Molecular Sciences
Volume19
Issue number8
DOIs
Publication statusPublished - Aug 7 2018

Fingerprint

activity (biology)
Bioactivity
Mycobacterium tuberculosis
Screening
tuberculosis
Spinacia oleracea
Benomyl
Electron Transport
Fungicides
Time and motion study
Methicillin
Staphylococcus aureus
Isoniazid
Biofilms
Antibiotics
Vancomycin
Ampicillin
synthesis
Cytotoxicity
Ciprofloxacin

Keywords

  • Activity relationship
  • Antifungal activity
  • Antistaphylococcal activity
  • Antitubercular activity
  • Biofilm
  • Cinnamamides
  • MTT assay
  • PET inhibition
  • Structure
  • Time-kill assay
  • Toxicity

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Pospisilova, S., Kos, J., Michnova, H., Kapustikova, I., Strharsky, T., Oravec, M., ... Jampilek, J. (2018). Synthesis and spectrum of biological activities of novel N-arylcinnamamides. International Journal of Molecular Sciences, 19(8), [2318]. https://doi.org/10.3390/ijms19082318

Synthesis and spectrum of biological activities of novel N-arylcinnamamides. / Pospisilova, Sarka; Kos, Jiri; Michnova, Hana; Kapustikova, Iva; Strharsky, Tomas; Oravec, Michal; Móricz, A.; Bakonyi, Jozsef; Kauerova, Tereza; Kollar, Peter; Cizek, Alois; Jampilek, Josef.

In: International Journal of Molecular Sciences, Vol. 19, No. 8, 2318, 07.08.2018.

Research output: Contribution to journalArticle

Pospisilova, S, Kos, J, Michnova, H, Kapustikova, I, Strharsky, T, Oravec, M, Móricz, A, Bakonyi, J, Kauerova, T, Kollar, P, Cizek, A & Jampilek, J 2018, 'Synthesis and spectrum of biological activities of novel N-arylcinnamamides', International Journal of Molecular Sciences, vol. 19, no. 8, 2318. https://doi.org/10.3390/ijms19082318
Pospisilova S, Kos J, Michnova H, Kapustikova I, Strharsky T, Oravec M et al. Synthesis and spectrum of biological activities of novel N-arylcinnamamides. International Journal of Molecular Sciences. 2018 Aug 7;19(8). 2318. https://doi.org/10.3390/ijms19082318
Pospisilova, Sarka ; Kos, Jiri ; Michnova, Hana ; Kapustikova, Iva ; Strharsky, Tomas ; Oravec, Michal ; Móricz, A. ; Bakonyi, Jozsef ; Kauerova, Tereza ; Kollar, Peter ; Cizek, Alois ; Jampilek, Josef. / Synthesis and spectrum of biological activities of novel N-arylcinnamamides. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 8.
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AU - Strharsky, Tomas

AU - Oravec, Michal

AU - Móricz, A.

AU - Bakonyi, Jozsef

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N2 - 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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KW - Antifungal activity

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KW - Antitubercular activity

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KW - MTT assay

KW - PET inhibition

KW - Structure

KW - Time-kill assay

KW - Toxicity

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