• Je něco špatně v tomto záznamu ?

Study of Biological Activities and ADMET-Related Properties of Salicylanilide-Based Peptidomimetics

D. Pindjakova, E. Pilarova, K. Pauk, H. Michnova, J. Hosek, P. Magar, A. Cizek, A. Imramovsky, J. Jampilek

. 2022 ; 23 (19) : . [pub] 20221001

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22033143

A series of eleven benzylated intermediates and eleven target compounds derived from salicylanilide were tested against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as reference strains and against three clinical isolates of methicillin-resistant S. aureus (MRSA) and three isolates of vancomycin-resistant E. faecalis. In addition, the compounds were evaluated against Mycobacterium tuberculosis H37Ra and M. smegmatis ATCC 700084. The in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line THP-1. The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. The benzylated intermediates were found to be completely biologically inactive. Of the final eleven compounds, according to the number of amide groups in the molecule, eight are diamides, and three are triamides that were inactive. 5-Chloro-2-hydroxy-N-[(2S)- 4-(methylsulfanyl)-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (3e) and 5-chloro-2-hydroxy-N-[(2S)-(4-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino)pentan-2-yl)benzamide (3f) showed the broadest spectrum of activity against all tested species/isolates comparable to the used standards (ampicillin and isoniazid). Six diamides showed high antistaphylococcal activity with MICs ranging from 0.070 to 8.95 μM. Three diamides showed anti-enterococcal activity with MICs ranging from 4.66 to 35.8 μM, and the activities of 3f and 3e against M. tuberculosis and M. smegmatis were MICs of 18.7 and 35.8 μM, respectively. All the active compounds were microbicidal. It was observed that the connecting linker between the chlorsalicylic and 4-CF3-anilide cores must be substituted with a bulky and/or lipophilic chain such as isopropyl, isobutyl, or thiabutyl chain. Anticancer activity on THP-1 cells IC50 ranged from 1.4 to >10 μM and increased with increasing lipophilicity.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22033143
003      
CZ-PrNML
005      
20230131150754.0
007      
ta
008      
230120s2022 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/ijms231911648 $2 doi
035    __
$a (PubMed)36232947
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Pindjakova, Dominika $u Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia
245    10
$a Study of Biological Activities and ADMET-Related Properties of Salicylanilide-Based Peptidomimetics / $c D. Pindjakova, E. Pilarova, K. Pauk, H. Michnova, J. Hosek, P. Magar, A. Cizek, A. Imramovsky, J. Jampilek
520    9_
$a A series of eleven benzylated intermediates and eleven target compounds derived from salicylanilide were tested against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as reference strains and against three clinical isolates of methicillin-resistant S. aureus (MRSA) and three isolates of vancomycin-resistant E. faecalis. In addition, the compounds were evaluated against Mycobacterium tuberculosis H37Ra and M. smegmatis ATCC 700084. The in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line THP-1. The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. The benzylated intermediates were found to be completely biologically inactive. Of the final eleven compounds, according to the number of amide groups in the molecule, eight are diamides, and three are triamides that were inactive. 5-Chloro-2-hydroxy-N-[(2S)- 4-(methylsulfanyl)-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (3e) and 5-chloro-2-hydroxy-N-[(2S)-(4-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino)pentan-2-yl)benzamide (3f) showed the broadest spectrum of activity against all tested species/isolates comparable to the used standards (ampicillin and isoniazid). Six diamides showed high antistaphylococcal activity with MICs ranging from 0.070 to 8.95 μM. Three diamides showed anti-enterococcal activity with MICs ranging from 4.66 to 35.8 μM, and the activities of 3f and 3e against M. tuberculosis and M. smegmatis were MICs of 18.7 and 35.8 μM, respectively. All the active compounds were microbicidal. It was observed that the connecting linker between the chlorsalicylic and 4-CF3-anilide cores must be substituted with a bulky and/or lipophilic chain such as isopropyl, isobutyl, or thiabutyl chain. Anticancer activity on THP-1 cells IC50 ranged from 1.4 to >10 μM and increased with increasing lipophilicity.
650    _2
$a ampicilin $7 D000667
650    _2
$a anilidy $7 D000813
650    _2
$a antibakteriální látky $x farmakologie $7 D000900
650    _2
$a benzamidy $7 D001549
650    _2
$a lidé $7 D006801
650    _2
$a isoniazid $7 D007538
650    12
$a methicilin rezistentní Staphylococcus aureus $7 D055624
650    _2
$a mikrobiální testy citlivosti $7 D008826
650    12
$a Mycobacterium tuberculosis $7 D009169
650    12
$a peptidomimetika $7 D057786
650    _2
$a salicylanilidy $x farmakologie $7 D012458
650    _2
$a vankomycin $7 D014640
655    _2
$a časopisecké články $7 D016428
700    1_
$a Pilarova, Eliska $u Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentska 95, 530 09 Pardubice, Czech Republic
700    1_
$a Pauk, Karel $u Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentska 95, 530 09 Pardubice, Czech Republic
700    1_
$a Michnova, Hana $u Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackeho tr. 1946/1, 612 42 Brno, Czech Republic
700    1_
$a Hosek, Jan $u Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic
700    1_
$a Magar, Pratibha $u Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentska 95, 530 09 Pardubice, Czech Republic
700    1_
$a Cizek, Alois $u Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackeho tr. 1946/1, 612 42 Brno, Czech Republic $1 https://orcid.org/0000000157064601
700    1_
$a Imramovsky, Ales $u Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentska 95, 530 09 Pardubice, Czech Republic $1 https://orcid.org/0000000194769627
700    1_
$a Jampilek, Josef $u Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia $u Department of Chemical Biology, Faculty of Science, Palacky University Olomouc, Slechtitelu 27, 783 71 Olomouc, Czech Republic $1 https://orcid.org/0000000320039052
773    0_
$w MED00176142 $t International journal of molecular sciences $x 1422-0067 $g Roč. 23, č. 19 (2022)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36232947 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230120 $b ABA008
991    __
$a 20230131150750 $b ABA008
999    __
$a ok $b bmc $g 1891731 $s 1184478
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2022 $b 23 $c 19 $e 20221001 $i 1422-0067 $m International journal of molecular sciences $n Int J Mol Sci $x MED00176142
LZP    __
$a Pubmed-20230120

Najít záznam

Citační ukazatele

Možnosti archivace