• Je něco špatně v tomto záznamu ?

Phenolic N-monosubstituted carbamates: Antitubercular and toxicity evaluation of multi-targeting compounds

M. Krátký, O. Janďourek, Z. Baranyai, E. Novotná, J. Stolaříková, S. Bősze, J. Vinšová,

. 2019 ; 181 (-) : 111578. [pub] 20190801

Jazyk angličtina Země Francie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc19044590

The research of novel antimycobacterial drugs represents a cutting-edge topic. Thirty phenolic N-monosubstituted carbamates, derivatives of salicylanilides and 4-chlorophenol, were investigated against Mycobacterium tuberculosis H37Ra, H37Rv including multidrug- and extensively drug-resistant strains, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium aurum and Mycobacterium smegmatis as representatives of nontuberculous mycobacteria (NTM) and for their cytotoxic and cytostatic properties in HepG2 cells. Since salicylanilides are multi-targeting compounds, we determined also inhibition of mycobacterial isocitrate lyase, an enzyme involved in the maintenance of persistent tuberculous infection. The minimum inhibitory concentrations were from ≤0.5 μM for both drug-susceptible and resistant M. tuberculosis and from ≤0.79 μM for NTM with no cross-resistance to established drugs. The presence of halogenated salicylanilide scaffold results into an improved activity. We have verified that isocitrate lyase is not a key target, presented carbamates showed only moderate inhibitory activity (up to 18% at a concentration of 10 μM). Most of the compounds showed no cytotoxicity for HepG2 cells and some of them were without cytostatic activity. Cytotoxicity-based selectivity indexes of several carbamates for M. tuberculosis, including resistant strains, were higher than 125, thus favouring some derivatives as promising features for future development.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19044590
003      
CZ-PrNML
005      
20200113081028.0
007      
ta
008      
200109s2019 fr f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.ejmech.2019.111578 $2 doi
035    __
$a (PubMed)31401536
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a fr
100    1_
$a Krátký, Martin $u Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic. Electronic address: martin.kratky@faf.cuni.cz.
245    10
$a Phenolic N-monosubstituted carbamates: Antitubercular and toxicity evaluation of multi-targeting compounds / $c M. Krátký, O. Janďourek, Z. Baranyai, E. Novotná, J. Stolaříková, S. Bősze, J. Vinšová,
520    9_
$a The research of novel antimycobacterial drugs represents a cutting-edge topic. Thirty phenolic N-monosubstituted carbamates, derivatives of salicylanilides and 4-chlorophenol, were investigated against Mycobacterium tuberculosis H37Ra, H37Rv including multidrug- and extensively drug-resistant strains, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium aurum and Mycobacterium smegmatis as representatives of nontuberculous mycobacteria (NTM) and for their cytotoxic and cytostatic properties in HepG2 cells. Since salicylanilides are multi-targeting compounds, we determined also inhibition of mycobacterial isocitrate lyase, an enzyme involved in the maintenance of persistent tuberculous infection. The minimum inhibitory concentrations were from ≤0.5 μM for both drug-susceptible and resistant M. tuberculosis and from ≤0.79 μM for NTM with no cross-resistance to established drugs. The presence of halogenated salicylanilide scaffold results into an improved activity. We have verified that isocitrate lyase is not a key target, presented carbamates showed only moderate inhibitory activity (up to 18% at a concentration of 10 μM). Most of the compounds showed no cytotoxicity for HepG2 cells and some of them were without cytostatic activity. Cytotoxicity-based selectivity indexes of several carbamates for M. tuberculosis, including resistant strains, were higher than 125, thus favouring some derivatives as promising features for future development.
650    _2
$a antituberkulotika $x chemická syntéza $x chemie $x farmakologie $7 D000995
650    _2
$a karbamáty $x chemická syntéza $x chemie $x farmakologie $7 D002219
650    _2
$a buňky Hep G2 $7 D056945
650    _2
$a lidé $7 D006801
650    _2
$a isocitrátlyasa $x antagonisté a inhibitory $x metabolismus $7 D007522
650    _2
$a Mycobacterium tuberculosis $x účinky léků $x enzymologie $7 D009169
650    _2
$a fenoly $x chemická syntéza $x chemie $x farmakologie $7 D010636
650    _2
$a salicylanilidy $x chemická syntéza $x chemie $x farmakologie $7 D012458
650    _2
$a tuberkulóza $x farmakoterapie $7 D014376
655    _2
$a časopisecké články $7 D016428
700    1_
$a Janďourek, Ondřej $u Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
700    1_
$a Baranyai, Zsuzsa $u MTA-ELTE Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, Budapest, H-1117, P.O. Box 32, 1518, Budapest 112, Hungary.
700    1_
$a Novotná, Eva $u Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
700    1_
$a Stolaříková, Jiřina $u Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské náměstí 7, 702 00, Ostrava, Czech Republic.
700    1_
$a Bősze, Szilvia $u MTA-ELTE Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, Budapest, H-1117, P.O. Box 32, 1518, Budapest 112, Hungary.
700    1_
$a Vinšová, Jarmila $u Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
773    0_
$w MED00001628 $t European journal of medicinal chemistry $x 1768-3254 $g Roč. 181, č. - (2019), s. 111578
856    41
$u https://pubmed.ncbi.nlm.nih.gov/31401536 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20200109 $b ABA008
991    __
$a 20200113081400 $b ABA008
999    __
$a ok $b bmc $g 1482859 $s 1083263
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2019 $b 181 $c - $d 111578 $e 20190801 $i 1768-3254 $m European journal of medicinal chemistry $n Eur J Med Chem $x MED00001628
LZP    __
$a Pubmed-20200109

Najít záznam

Citační ukazatele

Možnosti archivace