-
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
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
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
Free Medical Journals od 1997
PubMed Central od 2001
Europe PubMed Central od 2001
ProQuest Central od 1997-01-01
Open Access Digital Library od 1997-01-01
Medline Complete (EBSCOhost) od 2009-03-01
Health & Medicine (ProQuest) od 1997-01-01
Odkazy
PubMed
32408517
DOI
10.3390/molecules25102268
Knihovny.cz E-zdroje
- MeSH
- acetylcholinesterasa metabolismus MeSH
- antiinfekční látky * chemická syntéza chemie farmakologie MeSH
- buňky Hep G2 MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory * chemická syntéza chemie farmakologie MeSH
- GPI-vázané proteiny metabolismus MeSH
- imidazoly * chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- Mycobacterium avium růst a vývoj MeSH
- Mycobacterium kansasii růst a vývoj MeSH
- Mycobacterium tuberculosis růst a vývoj MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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