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

Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer's Disease Therapy

ÓM. Bautista-Aguilera, L. Ismaili, M. Chioua, R. Andrys, M. Schmidt, P. Bzonek, MÁ. Martínez-Grau, CD. Beadle, T. Vetman, F. López-Muñoz, I. Iriepa, B. Refouvelet, K. Musilek, J. Marco-Contelles

. 2020 ; 21 (11) : . [pub] 20200530

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc21012557

Grantová podpora
SAF2015-65586-R MINECO
UCJC 2020-03; UCJC 2020-33 UCJC
CZ.02.1.01/0.0/0.0/16_025/0007444 ERDF/ESF
SV2113-2019, VT2019-2021 University of Hradec Kralove
CA15135 MuTaLig EU COST

In this communication, we report the synthesis and cholinesterase (ChE)/monoamine oxidase (MAO) inhibition of 19 quinolinones (QN1-19) and 13 dihydroquinolinones (DQN1-13) designed as potential multitarget small molecules (MSM) for Alzheimer's disease therapy. Contrary to our expectations, none of them showed significant human recombinant MAO inhibition, but compounds QN8, QN9, and DQN7 displayed promising human recombinant acetylcholinesterase (hrAChE) and butyrylcholinesterase (hrBuChE) inhibition. In particular, molecule QN8 was found to be a potent and quite selective non-competitive inhibitor of hrAChE (IC50 = 0.29 μM), with Ki value in nanomolar range (79 nM). Pertinent docking analysis confirmed this result, suggesting that this ligand is an interesting hit for further investigation.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21012557
003      
CZ-PrNML
005      
20221101100438.0
007      
ta
008      
210420s2020 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/ijms21113913 $2 doi
035    __
$a (PubMed)32486316
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Bautista-Aguilera, Óscar M $u Department of Organic Chemistry and Inorganic Chemistry, Alcalá University, Alcalá de Henares, 28805 Madrid, Spain
245    10
$a Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer's Disease Therapy / $c ÓM. Bautista-Aguilera, L. Ismaili, M. Chioua, R. Andrys, M. Schmidt, P. Bzonek, MÁ. Martínez-Grau, CD. Beadle, T. Vetman, F. López-Muñoz, I. Iriepa, B. Refouvelet, K. Musilek, J. Marco-Contelles
520    9_
$a In this communication, we report the synthesis and cholinesterase (ChE)/monoamine oxidase (MAO) inhibition of 19 quinolinones (QN1-19) and 13 dihydroquinolinones (DQN1-13) designed as potential multitarget small molecules (MSM) for Alzheimer's disease therapy. Contrary to our expectations, none of them showed significant human recombinant MAO inhibition, but compounds QN8, QN9, and DQN7 displayed promising human recombinant acetylcholinesterase (hrAChE) and butyrylcholinesterase (hrBuChE) inhibition. In particular, molecule QN8 was found to be a potent and quite selective non-competitive inhibitor of hrAChE (IC50 = 0.29 μM), with Ki value in nanomolar range (79 nM). Pertinent docking analysis confirmed this result, suggesting that this ligand is an interesting hit for further investigation.
650    _2
$a acetylcholinesterasa $x metabolismus $7 D000110
650    _2
$a Alzheimerova nemoc $x farmakoterapie $7 D000544
650    _2
$a cholinesterasové inhibitory $x farmakologie $7 D002800
650    _2
$a racionální návrh léčiv $7 D015195
650    _2
$a preklinické hodnocení léčiv $7 D004353
650    _2
$a lidé $7 D006801
650    _2
$a inhibiční koncentrace 50 $7 D020128
650    _2
$a kinetika $7 D007700
650    _2
$a ligandy $7 D008024
650    _2
$a magnetická rezonanční spektroskopie $7 D009682
650    _2
$a simulace molekulového dockingu $7 D062105
650    _2
$a monoaminoxidasa $x metabolismus $7 D008995
650    _2
$a inhibitory MAO $x farmakologie $7 D008996
650    _2
$a chinolony $x farmakologie $7 D015363
650    _2
$a rekombinantní proteiny $x metabolismus $7 D011994
650    _2
$a vztahy mezi strukturou a aktivitou $7 D013329
655    _2
$a časopisecké články $7 D016428
700    1_
$a Ismaili, Lhassane $u Laboratoire de Chimie Organique et Thérapeutique, Neurosciences Intégratives et Cliniques EA 481, University Bourgogne Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000 Besançon, France
700    1_
$a Chioua, Mourad $u Laboratory of Medicinal Chemistry (IQOG, CSIC), C/ Juan de la Cierva 3, 28006 Madrid, Spain
700    1_
$a Andrys, Rudolf $u Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic
700    1_
$a Schmidt, Monika $u Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic $7 xx0278043
700    1_
$a Bzonek, Petr $u Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic
700    1_
$a Martínez-Grau, María Ángeles $u Lilly Research Laboratories, Eli Lilly & Company, Avda. de la Industria 30, Alcobendas, 28108 Madrid, Spain
700    1_
$a Beadle, Christopher D $u Lilly Research Centre, Eli Lilly & Company, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
700    1_
$a Vetman, Tatiana $u Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285, USA
700    1_
$a López-Muñoz, Francisco $u Faculty of Health, Camilo José Cela University of Madrid (UCJC), 28692 Villafranca del Castillo, Spain $u Neuropsychopharmacology Unit, "Hospital 12 de Octubre" Research Institute, 28041 Madrid, Spain
700    1_
$a Iriepa, Isabel $u Department of Organic Chemistry and Inorganic Chemistry, Alcalá University, Alcalá de Henares, 28805 Madrid, Spain $u Institute of Chemical Research Andrés M. del Río, Alcalá University, Alcalá de Henares, 28805 Madrid, Spain
700    1_
$a Refouvelet, Bernard $u Laboratoire de Chimie Organique et Thérapeutique, Neurosciences Intégratives et Cliniques EA 481, University Bourgogne Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000 Besançon, France
700    1_
$a Musilek, Kamil $u Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic
700    1_
$a Marco-Contelles, José $u Laboratory of Medicinal Chemistry (IQOG, CSIC), C/ Juan de la Cierva 3, 28006 Madrid, Spain
773    0_
$w MED00176142 $t International journal of molecular sciences $x 1422-0067 $g Roč. 21, č. 11 (2020)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32486316 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210420 $b ABA008
991    __
$a 20221101100435 $b ABA008
999    __
$a ok $b bmc $g 1650844 $s 1132936
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 21 $c 11 $e 20200530 $i 1422-0067 $m International journal of molecular sciences $n Int J Mol Sci $x MED00176142
GRA    __
$a SAF2015-65586-R $p MINECO
GRA    __
$a UCJC 2020-03; UCJC 2020-33 $p UCJC
GRA    __
$a CZ.02.1.01/0.0/0.0/16_025/0007444 $p ERDF/ESF
GRA    __
$a SV2113-2019, VT2019-2021 $p University of Hradec Kralove
GRA    __
$a CA15135 MuTaLig $p EU COST
LZP    __
$a Pubmed-20210420
Zpět

Najít záznam

Citační ukazatele

Možnosti archivace