Detail
Článek
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

N-Alkyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides and Their Analogues: Synthesis and Multitarget Biological Activity

M. Krátký, Z. Baranyai, Š. Štěpánková, K. Svrčková, M. Švarcová, J. Stolaříková, L. Horváth, S. Bősze, J. Vinšová

. 2020 ; 25 (10) : . [pub] 20200512

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc21012595

Grantová podpora
20-19638Y Grantová Agentura České Republiky
CZ.02.1.01/0.0/0.0/16_019/0000841 European Regional Development Fund
NKFIH-1157-8/2019-DT Eötvös Loránd Tudományegyetem

Based on the isosterism concept, we have designed and synthesized homologous N-alkyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides (from C1 to C18) as potential antimicrobial agents and enzyme inhibitors. They were obtained from 4-(trifluoromethyl)benzohydrazide by three synthetic approaches and characterized by spectral methods. The derivatives were screened for their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) via Ellman's method. All the hydrazinecarboxamides revealed a moderate inhibition of both AChE and BuChE, with IC50 values of 27.04-106.75 µM and 58.01-277.48 µM, respectively. Some compounds exhibited lower IC50 for AChE than the clinically used drug rivastigmine. N-Tridecyl/pentadecyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides were identified as the most potent and selective inhibitors of AChE. For inhibition of BuChE, alkyl chain lengths from C5 to C7 are optimal substituents. Based on molecular docking study, the compounds may work as non-covalent inhibitors that are placed in a close proximity to the active site triad. The compounds were evaluated against Mycobacterium tuberculosis H37Rv and nontuberculous mycobacteria (M. avium, M. kansasii). Reflecting these results, we prepared additional analogues of the most active carboxamide (n-hexyl derivative 2f). N-Hexyl-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-amine (4) exhibited the lowest minimum inhibitory concentrations within this study (MIC ≥ 62.5 µM), however, this activity is mild. All the compounds avoided cytostatic properties on two eukaryotic cell lines (HepG2, MonoMac6).

000      
00000naa a2200000 a 4500
001      
bmc21012595
003      
CZ-PrNML
005      
20210507103655.0
007      
ta
008      
210420s2020 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/molecules25102268 $2 doi
035    __
$a (PubMed)32408517
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
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
245    10
$a N-Alkyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides and Their Analogues: Synthesis and Multitarget Biological Activity / $c M. Krátký, Z. Baranyai, Š. Štěpánková, K. Svrčková, M. Švarcová, J. Stolaříková, L. Horváth, S. Bősze, J. Vinšová
520    9_
$a Based on the isosterism concept, we have designed and synthesized homologous N-alkyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides (from C1 to C18) as potential antimicrobial agents and enzyme inhibitors. They were obtained from 4-(trifluoromethyl)benzohydrazide by three synthetic approaches and characterized by spectral methods. The derivatives were screened for their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) via Ellman's method. All the hydrazinecarboxamides revealed a moderate inhibition of both AChE and BuChE, with IC50 values of 27.04-106.75 µM and 58.01-277.48 µM, respectively. Some compounds exhibited lower IC50 for AChE than the clinically used drug rivastigmine. N-Tridecyl/pentadecyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides were identified as the most potent and selective inhibitors of AChE. For inhibition of BuChE, alkyl chain lengths from C5 to C7 are optimal substituents. Based on molecular docking study, the compounds may work as non-covalent inhibitors that are placed in a close proximity to the active site triad. The compounds were evaluated against Mycobacterium tuberculosis H37Rv and nontuberculous mycobacteria (M. avium, M. kansasii). Reflecting these results, we prepared additional analogues of the most active carboxamide (n-hexyl derivative 2f). N-Hexyl-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-amine (4) exhibited the lowest minimum inhibitory concentrations within this study (MIC ≥ 62.5 µM), however, this activity is mild. All the compounds avoided cytostatic properties on two eukaryotic cell lines (HepG2, MonoMac6).
650    _2
$a acetylcholinesterasa $x metabolismus $7 D000110
650    12
$a antiinfekční látky $x chemická syntéza $x chemie $x farmakologie $7 D000890
650    _2
$a butyrylcholinesterasa $x metabolismus $7 D002091
650    12
$a cholinesterasové inhibitory $x chemická syntéza $x chemie $x farmakologie $7 D002800
650    _2
$a GPI-vázané proteiny $x metabolismus $7 D058851
650    _2
$a buňky Hep G2 $7 D056945
650    _2
$a lidé $7 D006801
650    12
$a imidazoly $x chemická syntéza $x chemie $x farmakologie $7 D007093
650    _2
$a Mycobacterium avium $x růst a vývoj $7 D009162
650    _2
$a Mycobacterium kansasii $x růst a vývoj $7 D019909
650    _2
$a Mycobacterium tuberculosis $x růst a vývoj $7 D009169
655    _2
$a časopisecké články $7 D016428
700    1_
$a Baranyai, Zsuzsa $u MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117, 1518 Budapest, Hungary
700    1_
$a Štěpánková, Šárka $u Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
700    1_
$a Svrčková, Katarína $u Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
700    1_
$a Švarcová, Markéta $u Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic $u Department of Chemistry, Faculty of Science, J. E. Purkinje University, České mládeže 8, 400 96 Ústí nad Labem, Czech Republic
700    1_
$a Stolaříková, Jiřina $u Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské námĕstí 7, 702 00 Ostrava, Czech Republic
700    1_
$a Horváth, Lilla $u MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117, 1518 Budapest, Hungary
700    1_
$a Bősze, Szilvia $u MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Pázmány Péter Sétány 1/A, H-1117, 1518 Budapest, 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 MED00180394 $t Molecules (Basel, Switzerland) $x 1420-3049 $g Roč. 25, č. 10 (2020)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32408517 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210420 $b ABA008
991    __
$a 20210507103654 $b ABA008
999    __
$a ok $b bmc $g 1650874 $s 1132974
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 25 $c 10 $e 20200512 $i 1420-3049 $m Molecules $n Molecules $x MED00180394
GRA    __
$a 20-19638Y $p Grantová Agentura České Republiky
GRA    __
$a CZ.02.1.01/0.0/0.0/16_019/0000841 $p European Regional Development Fund
GRA    __
$a NKFIH-1157-8/2019-DT $p Eötvös Loránd Tudományegyetem
LZP    __
$a Pubmed-20210420

Najít záznam

Citační ukazatele

Možnosti archivace