Trifluoromethylcinnamanilide Michael Acceptors for Treatment of
Resistant Bacterial Infections

J 2022

Trifluoromethylcinnamanilide Michael Acceptors for Treatment of Resistant Bacterial Infections

STRHÁRSKY, Tomáš, Dominika PINDJAKOVA, Jiří KOS, Lucia VRABLOVA, Pavel ŠMAK et. al.

Basic information

Original name

Trifluoromethylcinnamanilide Michael Acceptors for Treatment of Resistant Bacterial Infections

Authors

STRHÁRSKY, Tomáš (703 Slovakia, belonging to the institution), Dominika PINDJAKOVA, Jiří KOS (203 Czech Republic, guarantor, belonging to the institution), Lucia VRABLOVA, Pavel ŠMAK (203 Czech Republic, belonging to the institution), Hana MICHNOVA, Tomáš GONĚC (203 Czech Republic, belonging to the institution), Jan HOŠEK (203 Czech Republic), Michal ORAVEC, Izabela JENDRZEJEWSKA, Alois ČÍŽEK (203 Czech Republic) and Josef JAMPILEK

Edition

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2022, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.600

RIV identification code

RIV/00216224:14110/22:00127694

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/ijms232315090

UT WoS

000897240400001

Keywords in English

cinnamamides; Michael acceptors; antimicrobial activity; cytotoxicity; lipophilicity; structure-activity relationships; docking study

Abstract

V originále

A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2E)-3-[3-(Trifluoromethyl)phenyl]-N-[4-(trifluoromethyl)phenyl]prop-2-enamide (1j), (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide (1o) and (2E)-N-[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide (2i), (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide (2p) showed antistaphylococcal (MICs/MBCs 0.15-5.57 mu M) as well as anti-enterococcal (MICs/MBCs 2.34-44.5 mu M) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 mu M, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 mu M). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p, all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules.

Links

90123, large research infrastructures

Name: CzeCOS III

Citovat

STRHÁRSKY, Tomáš, Dominika PINDJAKOVA, Jiří KOS, Lucia VRABLOVA, Pavel ŠMAK, Hana MICHNOVA, Tomáš GONĚC, Jan HOŠEK, Michal ORAVEC, Izabela JENDRZEJEWSKA, Alois ČÍŽEK and Josef JAMPILEK. Trifluoromethylcinnamanilide Michael Acceptors for Treatment of Resistant Bacterial Infections. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2022, vol. 23, No 23, p. 1-22. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms232315090.

@article{2243548,
   author = {Strhársky, Tomáš and Pindjakova, Dominika and Kos, Jiří and Vrablova, Lucia and Šmak, Pavel and Michnova, Hana and Goněc, Tomáš and Hošek, Jan and Oravec, Michal and Jendrzejewska, Izabela and Čížek, Alois and Jampilek, Josef},
   article_location = {Basel},
   article_number = {23},
   doi = {http://dx.doi.org/10.3390/ijms232315090},
   keywords = {cinnamamides; Michael acceptors; antimicrobial activity; cytotoxicity; lipophilicity; structure-activity relationships; docking study},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Trifluoromethylcinnamanilide Michael Acceptors for Treatment of Resistant Bacterial Infections},
   url = {https://www.mdpi.com/1422-0067/23/23/15090},
   volume = {23},
   year = {2022}
}

TY  - JOUR
ID  - 2243548
AU  - Strhársky, Tomáš - Pindjakova, Dominika - Kos, Jiří - Vrablova, Lucia - Šmak, Pavel - Michnova, Hana - Goněc, Tomáš - Hošek, Jan - Oravec, Michal - Jendrzejewska, Izabela - Čížek, Alois - Jampilek, Josef
PY  - 2022
TI  - Trifluoromethylcinnamanilide Michael Acceptors for Treatment of Resistant Bacterial Infections
JF  - International Journal of Molecular Sciences
VL  - 23
IS  - 23
SP  - 1-22
EP  - 1-22
PB  - Multidisciplinary Digital Publishing Institute
SN  - 14220067
KW  - cinnamamides
KW  - Michael acceptors
KW  - antimicrobial activity
KW  - cytotoxicity
KW  - lipophilicity
KW  - structure-activity relationships
KW  - docking study
UR  - https://www.mdpi.com/1422-0067/23/23/15090
N2  - A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2E)-3-[3-(Trifluoromethyl)phenyl]-N-[4-(trifluoromethyl)phenyl]prop-2-enamide (1j), (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide (1o) and (2E)-N-[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide (2i), (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide (2p) showed antistaphylococcal (MICs/MBCs 0.15-5.57 mu M) as well as anti-enterococcal (MICs/MBCs 2.34-44.5 mu M) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 mu M, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 mu M). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p, all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules.
ER  -

STRHÁRSKY, Tomáš, Dominika PINDJAKOVA, Jiří KOS, Lucia VRABLOVA, Pavel ŠMAK, Hana MICHNOVA, Tomáš GONĚC, Jan HOŠEK, Michal ORAVEC, Izabela JENDRZEJEWSKA, Alois ČÍŽEK and Josef JAMPILEK. Trifluoromethylcinnamanilide Michael Acceptors for Treatment of Resistant Bacterial Infections. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2022, vol.~23, No~23, p.~1-22. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms232315090.

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