Next Article in Journal
Pin1 Modulation in Physiological Status and Neurodegeneration. Any Contribution to the Pathogenesis of Type 3 Diabetes?
Next Article in Special Issue
Novel Therapeutic Agent against Platelet Activation In Vitro and Arterial Thrombosis In Vivo by Morin Hydrate
Previous Article in Journal
PGC-1α Protects RPE Cells of the Aging Retina against Oxidative Stress-Induced Degeneration through the Regulation of Senescence and Mitochondrial Quality Control. The Significance for AMD Pathogenesis
Previous Article in Special Issue
Polyphenols Derived from Lychee Seed Suppress Aβ (1-42)-Induced Neuroinflammation
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(8), 2318; https://doi.org/10.3390/ijms19082318

Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia
2
Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic
3
Global Change Research Institute CAS, Belidla 986/4a, 60300 Brno, Czech Republic
4
Plant Protection Institute, Centre for Agricultural Research, Hungarian Academy of Sciences, Herman Otto Str. 15, 1022 Budapest, Hungary
5
Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic
*
Author to whom correspondence should be addressed.
Received: 9 July 2018 / Revised: 1 August 2018 / Accepted: 3 August 2018 / Published: 7 August 2018
(This article belongs to the Special Issue Plant Natural Products for Human Health)
View Full-Text   |   Download PDF [4181 KB, uploaded 8 August 2018]   |  

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. View Full-Text
Keywords: cinnamamides; antistaphylococcal activity; time-kill assay; biofilm; antitubercular activity; MTT assay; antifungal activity; PET inhibition; toxicity; structure–activity relationship cinnamamides; antistaphylococcal activity; time-kill assay; biofilm; antitubercular activity; MTT assay; antifungal activity; PET inhibition; toxicity; structure–activity relationship
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Pospisilova, S.; Kos, J.; Michnova, H.; Kapustikova, I.; Strharsky, T.; Oravec, M.; Moricz, A.M.; Bakonyi, J.; Kauerova, T.; Kollar, P.; Cizek, A.; Jampilek, J. Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides. Int. J. Mol. Sci. 2018, 19, 2318.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top