-
Je něco špatně v tomto záznamu ?
Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease
K. Chalupova, J. Korabecny, M. Bartolini, B. Monti, D. Lamba, R. Caliandro, A. Pesaresi, X. Brazzolotto, AJ. Gastellier, F. Nachon, J. Pejchal, M. Jarosova, V. Hepnarova, D. Jun, M. Hrabinova, R. Dolezal, J. Zdarova Karasova, M. Mzik, Z....
Jazyk angličtina Země Francie
Typ dokumentu časopisecké články
Odkazy
PubMed
30851693
DOI
10.1016/j.ejmech.2019.02.021
Knihovny.cz E-zdroje
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- amyloidní beta-protein antagonisté a inhibitory metabolismus MeSH
- bludiště - učení účinky léků MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- ligandy MeSH
- molekulární struktura MeSH
- neuroprotektivní látky chemická syntéza chemie farmakologie MeSH
- potkani Wistar MeSH
- proteinové agregáty účinky léků MeSH
- takrin chemie farmakologie MeSH
- tryptofan chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
A combination of tacrine and tryptophan led to the development of a new family of heterodimers as multi-target agents with potential to treat Alzheimer's disease. Based on the in vitro biological profile, compound S-K1035 was found to be the most potent inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), demonstrating balanced IC50 values of 6.3 and 9.1 nM, respectively. For all the tacrine-tryptophan heterodimers, favorable inhibitory effect on hAChE as well as on hBChE was coined to the optimal spacer length ranging from five to eight carbon atoms between these two pharmacophores. S-K1035 also showed good ability to inhibit Aβ42 self-aggregation (58.6 ± 5.1% at 50 μM) as well as hAChE-induced Aβ40 aggregation (48.3 ± 6.3% at 100 μM). The X-ray crystallographic analysis of TcAChE in complex with S-K1035 pinpointed the utility of the hybridization strategy applied and the structures determined with the two K1035 enantiomers in complex with hBChE could explain the higher inhibition potency of S-K1035. Other in vitro evaluations predicted the ability of S-K1035 to cross blood-brain barrier and to exert a moderate inhibition potency against neuronal nitric oxide synthase. Based on the initial promising biochemical data and a safer in vivo toxicity compared to tacrine, S-K1035 was administered to scopolamine-treated rats being able to dose-dependently revert amnesia.
Institute of Physiology Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic
National Institute of Mental Health Topolova 748 250 67 Klecany Czech Republic
- 000
- 00000naa a2200000 a 4500
- 001
- bmc19027735
- 003
- CZ-PrNML
- 005
- 20221014094716.0
- 007
- ta
- 008
- 190813s2019 fr f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.ejmech.2019.02.021 $2 doi
- 035 __
- $a (PubMed)30851693
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a fr
- 100 1_
- $a Chalupová, Katarína $u National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic; Department of Chemistry, University of Hradec Kralove, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic. $7 xx0245962
- 245 10
- $a Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease / $c K. Chalupova, J. Korabecny, M. Bartolini, B. Monti, D. Lamba, R. Caliandro, A. Pesaresi, X. Brazzolotto, AJ. Gastellier, F. Nachon, J. Pejchal, M. Jarosova, V. Hepnarova, D. Jun, M. Hrabinova, R. Dolezal, J. Zdarova Karasova, M. Mzik, Z. Kristofikova, J. Misik, L. Muckova, P. Jost, O. Soukup, M. Benkova, V. Setnicka, L. Habartova, M. Chvojkova, L. Kleteckova, K. Vales, E. Mezeiova, E. Uliassi, M. Valis, E. Nepovimova, ML. Bolognesi, K. Kuca,
- 520 9_
- $a A combination of tacrine and tryptophan led to the development of a new family of heterodimers as multi-target agents with potential to treat Alzheimer's disease. Based on the in vitro biological profile, compound S-K1035 was found to be the most potent inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), demonstrating balanced IC50 values of 6.3 and 9.1 nM, respectively. For all the tacrine-tryptophan heterodimers, favorable inhibitory effect on hAChE as well as on hBChE was coined to the optimal spacer length ranging from five to eight carbon atoms between these two pharmacophores. S-K1035 also showed good ability to inhibit Aβ42 self-aggregation (58.6 ± 5.1% at 50 μM) as well as hAChE-induced Aβ40 aggregation (48.3 ± 6.3% at 100 μM). The X-ray crystallographic analysis of TcAChE in complex with S-K1035 pinpointed the utility of the hybridization strategy applied and the structures determined with the two K1035 enantiomers in complex with hBChE could explain the higher inhibition potency of S-K1035. Other in vitro evaluations predicted the ability of S-K1035 to cross blood-brain barrier and to exert a moderate inhibition potency against neuronal nitric oxide synthase. Based on the initial promising biochemical data and a safer in vivo toxicity compared to tacrine, S-K1035 was administered to scopolamine-treated rats being able to dose-dependently revert amnesia.
- 650 _2
- $a acetylcholinesterasa $x metabolismus $7 D000110
- 650 _2
- $a Alzheimerova nemoc $x farmakoterapie $x metabolismus $7 D000544
- 650 _2
- $a amyloidní beta-protein $x antagonisté a inhibitory $x metabolismus $7 D016229
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a butyrylcholinesterasa $x metabolismus $7 D002091
- 650 _2
- $a cholinesterasové inhibitory $x chemická syntéza $x chemie $x farmakologie $7 D002800
- 650 _2
- $a vztah mezi dávkou a účinkem léčiva $7 D004305
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a ligandy $7 D008024
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a bludiště - učení $x účinky léků $7 D018782
- 650 _2
- $a molekulární struktura $7 D015394
- 650 _2
- $a neuroprotektivní látky $x chemická syntéza $x chemie $x farmakologie $7 D018696
- 650 _2
- $a proteinové agregáty $x účinky léků $7 D066329
- 650 _2
- $a krysa rodu Rattus $7 D051381
- 650 _2
- $a potkani Wistar $7 D017208
- 650 _2
- $a vztahy mezi strukturou a aktivitou $7 D013329
- 650 _2
- $a takrin $x chemie $x farmakologie $7 D013619
- 650 _2
- $a tryptofan $x chemie $x farmakologie $7 D014364
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Korabecny, Jan $u National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic; Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Bartolini, Manuela $u Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, I-40126, Bologna, Italy.
- 700 1_
- $a Monti, Barbara $u Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, I-40126, Bologna, Italy.
- 700 1_
- $a Lamba, Doriano $u Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Area Science Park - Basovizza, S.S. n° 14-Km 163.5, I-34149, Trieste, Italy.
- 700 1_
- $a Caliandro, Rosanna $u Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Area Science Park - Basovizza, S.S. n° 14-Km 163.5, I-34149, Trieste, Italy.
- 700 1_
- $a Pesaresi, Alessandro $u Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Area Science Park - Basovizza, S.S. n° 14-Km 163.5, I-34149, Trieste, Italy.
- 700 1_
- $a Brazzolotto, Xavier $u Institut de Recherche Biomédicale des Armées, Département de Toxicologie et Risques Chimiques, 1 Place Général Valérie André, 91220, Brétigny-sur-Orge, France.
- 700 1_
- $a Gastellier, Anne-Julie $u Institut de Recherche Biomédicale des Armées, Département de Toxicologie et Risques Chimiques, 1 Place Général Valérie André, 91220, Brétigny-sur-Orge, France.
- 700 1_
- $a Nachon, Florian $u Institut de Recherche Biomédicale des Armées, Département de Toxicologie et Risques Chimiques, 1 Place Général Valérie André, 91220, Brétigny-sur-Orge, France.
- 700 1_
- $a Pejchal, Jaroslav $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic.
- 700 1_
- $a Jarosova, Michaela $u Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Hepnarova, Vendula $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Jun, Daniel $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Hrabinova, Martina $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Dolezal, Rafael $u Department of Chemistry, University of Hradec Kralove, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Zdarova Karasova, Jana $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Mzik, Martin $u Institute of Clinical Biochemistry and Diagnosis, University Hospital, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Kristofikova, Zdena $u National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic.
- 700 1_
- $a Misik, Jan $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Muckova, Lubica $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic.
- 700 1_
- $a Jost, Petr $u Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Soukup, Ondrej $u National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic; Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Benkova, Marketa $u Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
- 700 1_
- $a Setnicka, Vladimir $u Department of Analytical Chemistry, University of Chemistry and Technology Prague, Technicka 5, 166 28, Prague, Czech Republic.
- 700 1_
- $a Habartova, Lucie $u Department of Analytical Chemistry, University of Chemistry and Technology Prague, Technicka 5, 166 28, Prague, Czech Republic.
- 700 1_
- $a Chvojkova, Marketa $u National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic; Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 142 20, Prague, Czech Republic.
- 700 1_
- $a Kleteckova, Lenka $u National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic; Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 142 20, Prague, Czech Republic.
- 700 1_
- $a Vales, Karel $u National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic; Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 142 20, Prague, Czech Republic.
- 700 1_
- $a Mezeiová, Eva $u National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic. $7 xx0277560
- 700 1_
- $a Uliassi, Elisa $u Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, I-40126, Bologna, Italy.
- 700 1_
- $a Valis, Martin $u Department of Neurology, Charles University in Prague, Faculty of Medicine in Hradec Kralove and University Hospital, Simkova 870, 500 03, Hradec Kralove, Czech Republic.
- 700 1_
- $a Nepovimova, Eugenie $u Department of Chemistry, University of Hradec Kralove, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic.
- 700 1_
- $a Bolognesi, Maria Laura $u Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, I-40126, Bologna, Italy. Electronic address: marialaura.bolognesi@unibo.it.
- 700 1_
- $a Kuca, Kamil $u Department of Chemistry, University of Hradec Kralove, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic. Electronic address: kamil.kuca@fnhk.cz.
- 773 0_
- $w MED00001628 $t European journal of medicinal chemistry $x 1768-3254 $g Roč. 168, č. - (2019), s. 491-514
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/30851693 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20190813 $b ABA008
- 991 __
- $a 20221014094709 $b ABA008
- 999 __
- $a ok $b bmc $g 1432884 $s 1066195
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2019 $b 168 $c - $d 491-514 $e 20190227 $i 1768-3254 $m European journal of medicinal chemistry $n Eur J Med Chem $x MED00001628
- LZP __
- $a Pubmed-20190813