Study of Biological Activities and ADMET-Related Properties of
Novel Chlorinated N-arylcinnamamides

J 2022

Study of Biological Activities and ADMET-Related Properties of Novel Chlorinated N-arylcinnamamides

STRHARSKY, Tomas, Dominika PINDJAKOVA, Jiří KOS, Lucia VRABLOVA, Hana MICHNOVA et. al.

Basic information

Original name

Study of Biological Activities and ADMET-Related Properties of Novel Chlorinated N-arylcinnamamides

Authors

STRHARSKY, Tomas (203 Czech Republic), Dominika PINDJAKOVA, Jiří KOS (203 Czech Republic, belonging to the institution), Lucia VRABLOVA, Hana MICHNOVA (203 Czech Republic), Jan HOSEK (203 Czech Republic), Nicol STRAKOVA (203 Czech Republic), Veronika LELAKOVA (203 Czech Republic), Lenka LEVA (203 Czech Republic), Lenka KAVANOVA (203 Czech Republic), Michal ORAVEC (203 Czech Republic), Alois CIZEK (203 Czech Republic) and Josef JAMPILEK (203 Czech Republic)

Edition

International Journal of Molecular Sciences, Basel, MDPI, 2022, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.600

RIV identification code

RIV/00216224:14110/22:00125675

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/ijms23063159

UT WoS

000775429300001

Keywords in English

cinnamamides; antimicrobial activity; cytotoxicity; lipophilicity; structure-activity relationships

Abstract

V originále

A series of eighteen 4-chlorocinnamanilides and eighteen 3,4-dichlorocinnamanilides were designed, prepared and characterized. All compounds were evaluated for their activity against gram-positive bacteria and against two mycobacterial strains. Viability on both cancer and primary mammalian cell lines was also assessed. The lipophilicity of the compounds was experimentally determined and correlated together with other physicochemical properties of the prepared derivatives with biological activity. 3,4-Dichlorocinnamanilides showed a broader spectrum of action and higher antibacterial efficacy than 4-chlorocinnamanilides; however, all compounds were more effective or comparable to clinically used drugs (ampicillin, isoniazid, rifampicin). Of the thirty-six compounds, six derivatives showed submicromolar activity against Staphylococcus aureus and clinical isolates of methicillin-resistant S. aureus (MRSA). (2E)-N-[3,5-bis(trifluoromethyl)phenyl]- 3-(4-chlorophenyl)prop-2-enamide was the most potent in series 1. (2E)-N-[3,5-bis(Trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-enamide, (2E)-3-(3,4-dichlorophenyl)-N-[3-(trifluoromethyl)phenyl]prop-2-enamide, (2E)-3-(3,4-dichloro- phenyl)-N-[4-(trifluoromethyl)phenyl]prop-2-enamide and (2E)-3-(3,4-dichlorophenyl)- N-[4-(trifluoromethoxy)phenyl]prop-2-enamide were the most active in series 2 and in addition to activity against S. aureus and MRSA were highly active against Enterococcus faecalis and vancomycin-resistant E. faecalis isolates and against fast-growing Mycobacterium smegmatis and against slow-growing M. marinum, M. tuberculosis non-hazardous test models. In addition, the last three compounds of the above-mentioned showed insignificant cytotoxicity to primary porcine monocyte-derived macrophages.

Links

90123, large research infrastructures

Name: CzeCOS III

Citovat

STRHARSKY, Tomas, Dominika PINDJAKOVA, Jiří KOS, Lucia VRABLOVA, Hana MICHNOVA, Jan HOSEK, Nicol STRAKOVA, Veronika LELAKOVA, Lenka LEVA, Lenka KAVANOVA, Michal ORAVEC, Alois CIZEK and Josef JAMPILEK. Study of Biological Activities and ADMET-Related Properties of Novel Chlorinated N-arylcinnamamides. International Journal of Molecular Sciences. Basel: MDPI, 2022, vol. 23, No 6, p. 1-20. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms23063159.

@article{1847637,
   author = {Strharsky, Tomas and Pindjakova, Dominika and Kos, Jiří and Vrablova, Lucia and Michnova, Hana and Hosek, Jan and Strakova, Nicol and Lelakova, Veronika and Leva, Lenka and Kavanova, Lenka and Oravec, Michal and Cizek, Alois and Jampilek, Josef},
   article_location = {Basel},
   article_number = {6},
   doi = {http://dx.doi.org/10.3390/ijms23063159},
   keywords = {cinnamamides; antimicrobial activity; cytotoxicity; lipophilicity; structure-activity relationships},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Study of Biological Activities and ADMET-Related Properties of Novel Chlorinated N-arylcinnamamides},
   url = {https://www.mdpi.com/1422-0067/23/6/3159},
   volume = {23},
   year = {2022}
}

TY  - JOUR
ID  - 1847637
AU  - Strharsky, Tomas - Pindjakova, Dominika - Kos, Jiří - Vrablova, Lucia - Michnova, Hana - Hosek, Jan - Strakova, Nicol - Lelakova, Veronika - Leva, Lenka - Kavanova, Lenka - Oravec, Michal - Cizek, Alois - Jampilek, Josef
PY  - 2022
TI  - Study of Biological Activities and ADMET-Related Properties of Novel Chlorinated N-arylcinnamamides
JF  - International Journal of Molecular Sciences
VL  - 23
IS  - 6
SP  - 1-20
EP  - 1-20
PB  - MDPI
SN  - 14220067
KW  - cinnamamides
KW  - antimicrobial activity
KW  - cytotoxicity
KW  - lipophilicity
KW  - structure-activity relationships
UR  - https://www.mdpi.com/1422-0067/23/6/3159
N2  - A series of eighteen 4-chlorocinnamanilides and eighteen 3,4-dichlorocinnamanilides were designed, prepared and characterized. All compounds were evaluated for their activity against gram-positive bacteria and against two mycobacterial strains. Viability on both cancer and primary mammalian cell lines was also assessed. The lipophilicity of the compounds was experimentally determined and correlated together with other physicochemical properties of the prepared derivatives with biological activity. 3,4-Dichlorocinnamanilides showed a broader spectrum of action and higher antibacterial efficacy than 4-chlorocinnamanilides; however, all compounds were more effective or comparable to clinically used drugs (ampicillin, isoniazid, rifampicin). Of the thirty-six compounds, six derivatives showed submicromolar activity against Staphylococcus aureus and clinical isolates of methicillin-resistant S. aureus (MRSA). (2E)-N-[3,5-bis(trifluoromethyl)phenyl]- 3-(4-chlorophenyl)prop-2-enamide was the most potent in series 1. (2E)-N-[3,5-bis(Trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-enamide, (2E)-3-(3,4-dichlorophenyl)-N-[3-(trifluoromethyl)phenyl]prop-2-enamide, (2E)-3-(3,4-dichloro- phenyl)-N-[4-(trifluoromethyl)phenyl]prop-2-enamide and (2E)-3-(3,4-dichlorophenyl)- N-[4-(trifluoromethoxy)phenyl]prop-2-enamide were the most active in series 2 and in addition to activity against S. aureus and MRSA were highly active against Enterococcus faecalis and vancomycin-resistant E. faecalis isolates and against fast-growing Mycobacterium smegmatis and against slow-growing M. marinum, M. tuberculosis non-hazardous test models. In addition, the last three compounds of the above-mentioned showed insignificant cytotoxicity to primary porcine monocyte-derived macrophages.
ER  -

STRHARSKY, Tomas, Dominika PINDJAKOVA, Jiří KOS, Lucia VRABLOVA, Hana MICHNOVA, Jan HOSEK, Nicol STRAKOVA, Veronika LELAKOVA, Lenka LEVA, Lenka KAVANOVA, Michal ORAVEC, Alois CIZEK and Josef JAMPILEK. Study of Biological Activities and ADMET-Related Properties of Novel Chlorinated N-arylcinnamamides. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2022, vol.~23, No~6, p.~1-20. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms23063159.

Detailed Information on Publication Record