• Something wrong with this record ?

Design, Synthesis and Antimicrobial Evaluation of New N-(1-Hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)(hetero)aryl-2-carboxamides as Potential Inhibitors of Mycobacterial Leucyl-tRNA Synthetase

P. Šlechta, AA. Needle, O. Jand'ourek, P. Paterová, K. Konečná, P. Bárta, J. Kuneš, V. Kubíček, M. Doležal, M. Kučerová-Chlupáčová

. 2023 ; 24 (3) : . [pub] 20230202

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc23004260

Tuberculosis remains a serious killer among infectious diseases due to its incidence, mortality, and occurrence of resistant mycobacterial strains. The challenge to discover new antimycobacterial agents forced us to prepare a series of N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)(hetero)aryl-2-carboxamides 1-19 via the acylation of 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol with various activated (hetero)arylcarboxylic acids. These novel compounds have been tested in vitro against a panel of clinically important fungi and bacteria, including mycobacteria. Some of the compounds inhibited the growth of mycobacteria in the range of micromolar concentrations and retained this activity also against multidrug-resistant clinical isolates. Half the maximal inhibitory concentrations against the HepG2 cell line indicated an acceptable toxicological profile. No growth inhibition of other bacteria and fungi demonstrated selectivity of the compounds against mycobacteria. The structure-activity relationships have been derived and supported with a molecular docking study, which confirmed a selectivity toward the potential target leucyl-tRNA synthetase without an impact on the human enzyme. The presented compounds can become important materials in antimycobacterial research.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc23004260
003      
CZ-PrNML
005      
20250305132156.0
007      
ta
008      
230418s2023 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/ijms24032951 $2 doi
035    __
$a (PubMed)36769275
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Šlechta, Petr $u Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic $1 https://orcid.org/0000000278149353 $7 xx0329837
245    10
$a Design, Synthesis and Antimicrobial Evaluation of New N-(1-Hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)(hetero)aryl-2-carboxamides as Potential Inhibitors of Mycobacterial Leucyl-tRNA Synthetase / $c P. Šlechta, AA. Needle, O. Jand'ourek, P. Paterová, K. Konečná, P. Bárta, J. Kuneš, V. Kubíček, M. Doležal, M. Kučerová-Chlupáčová
520    9_
$a Tuberculosis remains a serious killer among infectious diseases due to its incidence, mortality, and occurrence of resistant mycobacterial strains. The challenge to discover new antimycobacterial agents forced us to prepare a series of N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)(hetero)aryl-2-carboxamides 1-19 via the acylation of 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol with various activated (hetero)arylcarboxylic acids. These novel compounds have been tested in vitro against a panel of clinically important fungi and bacteria, including mycobacteria. Some of the compounds inhibited the growth of mycobacteria in the range of micromolar concentrations and retained this activity also against multidrug-resistant clinical isolates. Half the maximal inhibitory concentrations against the HepG2 cell line indicated an acceptable toxicological profile. No growth inhibition of other bacteria and fungi demonstrated selectivity of the compounds against mycobacteria. The structure-activity relationships have been derived and supported with a molecular docking study, which confirmed a selectivity toward the potential target leucyl-tRNA synthetase without an impact on the human enzyme. The presented compounds can become important materials in antimycobacterial research.
650    _2
$a lidé $7 D006801
650    12
$a aminoacyl-tRNA-synthetasy $7 D000604
650    _2
$a antibakteriální látky $x farmakologie $7 D000900
650    12
$a antiinfekční látky $x farmakologie $7 D000890
650    _2
$a antituberkulotika $x farmakologie $7 D000995
650    _2
$a houby $7 D005658
650    _2
$a mikrobiální testy citlivosti $7 D008826
650    _2
$a simulace molekulového dockingu $7 D062105
650    12
$a Mycobacterium tuberculosis $7 D009169
650    _2
$a vztahy mezi strukturou a aktivitou $7 D013329
650    _2
$a amidy $x chemie $x farmakologie $7 D000577
655    _2
$a časopisecké články $7 D016428
700    1_
$a Needle, Adam Anthony $u Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic
700    1_
$a Jand'ourek, Ondřej $u Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic $1 https://orcid.org/0000000346332062 $7 xx0230412
700    1_
$a Paterová, Pavla $u Department of Clinical Microbiology, University Hospital, 500 05 Hradec Králové, Czech Republic $1 https://orcid.org/0000000301927345 $7 xx0138094
700    1_
$a Konečná, Klára $u Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic $1 https://orcid.org/0000000156707767 $7 uk20201094799
700    1_
$a Bárta, Pavel $u Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic $1 https://orcid.org/0000000154455658 $7 uk20211104475
700    1_
$a Kuneš, Jiří $u Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic
700    1_
$a Kubíček, Vladimír $u Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic
700    1_
$a Doležal, Martin $u Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic $1 https://orcid.org/0000000315586625 $7 jn19981000714
700    1_
$a Kučerová-Chlupáčová, Marta $u Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic $1 https://orcid.org/0000000286560740 $7 uk20201095433
773    0_
$w MED00176142 $t International journal of molecular sciences $x 1422-0067 $g Roč. 24, č. 3 (2023)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36769275 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230418 $b ABA008
991    __
$a 20250305132206 $b ABA008
999    __
$a ok $b bmc $g 1924746 $s 1190469
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2023 $b 24 $c 3 $e 20230202 $i 1422-0067 $m International journal of molecular sciences $n Int J Mol Sci $x MED00176142
LZP    __
$a Pubmed-20230418

Find record

Citation metrics

Archiving options