Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides.

Autor: Pospisilova S; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia. sharka.pospisilova@gmail.com.; Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic. sharka.pospisilova@gmail.com., Kos J; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia. jirikos85@gmail.com., Michnova H; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia. michnova.hana@gmail.com.; Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic. michnova.hana@gmail.com., Kapustikova I; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia. kapustikova@fpharm.uniba.sk., Strharsky T; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia. strharsky2@uniba.sk., Oravec M; Global Change Research Institute CAS, Belidla 986/4a, 60300 Brno, Czech Republic. oravec.m@czechglobe.cz., Moricz AM; Plant Protection Institute, Centre for Agricultural Research, Hungarian Academy of Sciences, Herman Otto Str. 15, 1022 Budapest, Hungary. moricz.agnes@agrar.mta.hu., Bakonyi J; Plant Protection Institute, Centre for Agricultural Research, Hungarian Academy of Sciences, Herman Otto Str. 15, 1022 Budapest, Hungary. bakonyi.jozsef@agrar.mta.hu., Kauerova T; Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic. tereza.kauerova@gmail.com., Kollar P; Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic. kollarp@vfu.cz., Cizek A; Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic. cizeka@vfu.cz., Jampilek J; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia. josef.jampilek@gmail.com.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2018 Aug 07; Vol. 19 (8). Date of Electronic Publication: 2018 Aug 07.
DOI: 10.3390/ijms19082318
Abstrakt: : 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. (2 E )- N -[3,5-bis(trifluoromethyl)phenyl]-3-phenylprop-2-enamide and (2 E )-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. (2 E )- N -(3,5-Dichlorophenyl)- and (2 E )- 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. (2 E )- N -(3-Fluorophenyl)- and (2 E )- 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. (2 E )- N -(3,5-dichlorophenyl)-3-phenylprop-2-enamide (IC 50 = 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.
Competing Interests: The authors declare no conflicts of interest.
Databáze: MEDLINE
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