Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides

• Published in: International journal of molecular sciences Vol. 19; no. 8; p. 2318
• Main Authors: Pospisilova, Sarka, Kos, Jiri, Michnova, Hana, Kapustikova, Iva, Strharsky, Tomas, Oravec, Michal, Moricz, Agnes M, Bakonyi, Jozsef, Kauerova, Tereza, Kollar, Peter, Cizek, Alois, Jampilek, Josef
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07-08-2018; MDPI
• Subjects: Ampicillin; Antibiotics; Antifungal activity; antistaphylococcal activity; antitubercular activity; Benomyl; Biocompatibility; biofilm; Biofilms; Chloroplasts; cinnamamides; Ciprofloxacin; Cytotoxicity; Drug resistance; Electron transport; Fungicides; Isoniazid; Metabolism; Methicillin; Minimum inhibitory concentration; MTT assay; PET inhibition; Photosynthesis; Spinach; Staphylococcus aureus; structure–activity relationship; time-kill assay; toxicity; Tuberculosis; Vancomycin; cinnamamides; toxicity; time-kill assay; antistaphylococcal activity; biofilm; structure–activity relationship; antitubercular activity; PET inhibition; MTT assay; antifungal activity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19082318

A series of sixteen ring-substituted
-arylcinnamamides was prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against
, three methicillin-resistant
strains,
H37Ra,
, and
. Several of the tested compounds showed antistaphylococcal, antitubercular, and antifungal activities comparable with or higher than those of ampicillin, isoniazid, and benomyl. (2
)-
-[3,5-bis(trifluoromethyl)phenyl]-3-phenylprop-2-enamide and (2
)-3-phenyl-
-[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
. These compounds showed an activity against biofilm formation of
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
)-
-(3,5-Dichlorophenyl)- and (2
)-
-(3,4-dichlorophenyl)-3-phenylprop-2-enamide had a MIC = 27.38 µM against
, while a significant decrease (22.65%) of mycobacterial cell metabolism determined by the MTT assay was observed for the 3,5-dichlorophenyl derivative. (2
)-
-(3-Fluorophenyl)- and (2
)-
-(3-methylphenyl)-3-phenylprop-2-enamide exhibited MICs = 16.58 and 33.71 µM, respectively, against
.
. 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 (
L.) chloroplasts. (2
)-
-(3,5-dichlorophenyl)-3-phenylprop-2-enamide (IC
= 5.1 µM) was the most active PET inhibitor. Compounds with fungicide potency did not show any in vivo toxicity against
var. Samsun. The structure⁻activity relationships are discussed.