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N-Arylcinnamamides as antistaphylococcal agents
* 1 , 2 , 2, 3 , 2 , 3 , * 2
1  Division of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacky University, Slechtitelu 27, 78371 Olomouc, Czech Republic
2  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia
3  Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic

Published: 31 October 2018 by MDPI in 4th International Electronic Conference on Medicinal Chemistry session ECMC-4

Despite the fact that the percentage of methicillin-resistant Staphylococcus aureus is slowly decreasing in Europe [1], new compounds for fighting bacterial infections are still needed. Biofilm-associated infections, which are a significant cause of mortality, are also considered a serious problem [2]. Derivatives of cinnamic acid have been investigated for a long time due to their wide spectrum of biological activities, such as antibacterial, antiviral, antidiabetic, anxiolytic and anti-inflammatory [3].

Based on these facts, a series of 16 ring-substituted N-arylcinnamamides was synthetized and investigated for their antibacterial activity against S. aureus ATCC 29213 and 3 methicillin-resistant isolates. The microtitration dilution method was used for the determination of minimum inhibitory concentration (MIC). In addition, the most potent compounds were studied for their synergetic effect with clinically used antibacterial chemotherapeutics and ability to inhibit and degrade staphylococcal biofilm; in addition, the dynamics of their antibacterial activity was characterized.

(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. These compounds showed an activity against biofilm formation of S. aureus ATCC 29213 in concentrations close to MICs, but no degradative effect on mature biofilm was observed. Both compounds showed abilities to increase the activity of clinically used antibiotics with different mechanisms of action (vancomycin, ciprofloxacin and tetracycline). In time-kill studies, a decrease of colony-forming units (CFU/mL) of >99% was observed after 8 h from the beginning of incubation.

This contribution was supported by grant No. UK/229/2018 of the Comenius University in Bratislava, grants FaF UK/9/2018 and FaF UK/37/2018 of the Faculty of Pharmacy of Comenius University in Bratislava and partially by SANOFI-AVENTIS Pharma Slovakia, s.r.o.

  1. HEUER, O. et al. Antimicrobial resistance surveillance in Europe: annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). European Centre for Disease Prevention and Control (ECDC), 2010.
  2. SON, J.S. et al. Antibacterial and biofilm removal activity of a podoviridae Staphylococcus aureus bacteriophage SAP-2 and a derived recombinant cell-wall-degrading enzyme. Microbiol. Biotechnol. 2010. 86, 1439-1449.
  3. POSPISILOVA, S. et al. Synthesis and spectrum of biological activities of novel N‑arylcinnamamides. J. Mol. Sci. 2018, 19, 2318.
Keywords: Staphylococcus aureus; biofilm; time-kill; antibacterial; cinnamic acid; cinnamamides; synergy