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dc.contributor.author |
Kratky, Martin
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cze |
dc.contributor.author |
Baranyai, Zsuzsa
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dc.contributor.author |
Štěpánková, Šárka
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dc.contributor.author |
Svrčková, Katarína
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dc.contributor.author |
Svarcova, Marketa
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dc.contributor.author |
Stolarikova, Jirina
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dc.contributor.author |
Horvath, Lilla
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dc.contributor.author |
Bosze, Szilvia
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dc.contributor.author |
Vinsova, Jarmila
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dc.date.accessioned |
2021-05-15T18:29:50Z |
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dc.date.available |
2021-05-15T18:29:50Z |
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dc.date.issued |
2020 |
eng |
dc.identifier.issn |
1420-3049 |
eng |
dc.identifier.uri |
https://hdl.handle.net/10195/77169 |
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dc.description.abstract |
Based on the isosterism concept, we have designed and synthesized homologous N-alkyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides (from C-1 to C-18) 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 mu M and 58.01-277.48 mu M, 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 C-5 to C-7 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 H(37)Rv 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 mu M), however, this activity is mild. All the compounds avoided cytostatic properties on two eukaryotic cell lines (HepG2, MonoMac6). |
eng |
dc.format |
p. 2268 |
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dc.language.iso |
eng |
eng |
dc.publisher |
MDPI |
eng |
dc.relation.ispartof |
Molecules, volume 25, issue: 10 |
eng |
dc.rights |
open access (CC BY 4.0) |
eng |
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
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dc.subject |
antimycobacterial activity |
eng |
dc.subject |
acetylcholinesterase inhibition |
eng |
dc.subject |
butyrylcholinesterase inhibition |
eng |
dc.subject |
cytostatic properties |
eng |
dc.subject |
hydrazides |
eng |
dc.subject |
4-(trifluoromethyl)benzohydrazide |
eng |
dc.subject |
antimykobakteriální aktivita |
cze |
dc.subject |
inhibice acetylcholinesterázy |
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dc.subject |
inhibice butyrylcholinesterázy |
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dc.subject |
cytostatické vlastnosti |
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dc.subject |
hydrazidy |
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dc.subject |
4- (trifluormethyl) benzohydrazid |
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dc.title |
N-Alkyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides and Their Analogues: Synthesis and Multitarget Biological Activity |
eng |
dc.title.alternative |
N-Alkyl-2- [4- (trifluormethyl) benzoyl] hydrazin-1-karboxamidy a jejich analogy: Syntéza a vícebarevná biologická aktivita |
cze |
dc.type |
article |
eng |
dc.description.abstract-translated |
Na základě konceptu isosterismu jsme navrhli a syntetizovali homologní N-alkyl-2- [4- (trifluormethyl) benzoyl] hydrazin-1-karboxamidy (od C-1 do C-18) jako potenciální antimikrobiální látky a inhibitory enzymů. Byly získány z 4- (trifluormethyl) benzohydrazidu třemi syntetickými přístupy a charakterizovány spektrálními metodami. U derivátů se pomocí Ellmanovy metody zkoumala jejich inhibice acetylcholinesterázy (AChE) a butyrylcholinesterázy (BuChE). Všechny hydrazinkarboxamidy odhalily mírnou inhibici jak AChE, tak BuChE, s hodnotami IC50 27,04 - 106,75 uM a 58,01 - 277,48 uM. Některé sloučeniny vykazovaly nižší IC50 pro AChE než klinicky používané léčivo rivastigmin. Jako nejúčinnější a nejselektivnější inhibitory AChE byly identifikovány N-tridecyl / pentadecyl-2- [4- (trifluormethyl) benzoyl] hydrazin-1-karboxamidy. Pro inhibici BuChE jsou optimálními substituenty délky alkylového řetězce od C-5 do C-7. Na základě studie molekulárního dokování mohou sloučeniny fungovat jako nekovalentní inhibitory, které jsou umístěny v těsné blízkosti triády aktivního místa. Sloučeniny byly hodnoceny proti Mycobacterium tuberculosis H (37) Rv a proti netuberkulózním mykobakteriím (M. avium, M. kansasii). Na základě těchto výsledků jsme připravili další analogy nejaktivnějšího karboxamidu (n-hexyl derivát 2f). N-Hexyl-5- [4- (trifluormethyl) fenyl] -1,3,4-oxadiazol-2-amin (4) vykazoval nejnižší minimální inhibiční koncentrace v rámci této studie (MIC> = 62,5 uM), nicméně toto aktivita je mírná. Všechny sloučeniny se vyhýbaly cytostatickým vlastnostem na dvou eukaryotických buněčných liniích (HepG2, MonoMac6). |
cze |
dc.peerreviewed |
yes |
eng |
dc.publicationstatus |
published version |
eng |
dc.identifier.doi |
10.3390/molecules25102268 |
eng |
dc.relation.publisherversion |
https://www.mdpi.com/1420-3049/25/10/2268 |
eng |
dc.identifier.wos |
000539293400001 |
eng |
dc.identifier.scopus |
2-s2.0-85085157363 |
|
dc.identifier.obd |
39884698 |
eng |
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