-
Je něco špatně v tomto záznamu ?
Hydroxy-substituted trans-cinnamoyl derivatives as multifunctional tools in the context of Alzheimer's disease
A. De Simone, M. Bartolini, A. Baschieri, KYP. Apperley, HH. Chen, M. Guardigni, S. Montanari, T. Kobrlova, O. Soukup, L. Valgimigli, V. Andrisano, JW. Keillor, M. Basso, A. Milelli,
Jazyk angličtina Země Francie
Typ dokumentu časopisecké články
- MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- cinnamáty chemická syntéza chemie farmakologie MeSH
- GSK3B antagonisté a inhibitory metabolismus MeSH
- molekulární struktura MeSH
- scavengery volných radikálů chemická syntéza chemie farmakologie MeSH
- stereoizomerie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (Aβ), glycogen synthase kinase 3β (GSK-3β) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments. We designed compound 3 which demonstrated the ability to inhibit both GSK-3β (IC50 = 24.36 ± 0.01 μM) and Aβ42 self-aggregation (IC50 = 9.0 ± 1.4 μM), to chelate copper (II) and to act as exceptionally strong radical scavenger (kinh = 6.8 ± 0.5 · 105 M-1s-1) even in phosphate buffer at pH 7.4 (kinh = 3.2 ± 0.5 · 105 M-1s-1). Importantly, compound 3 showed high-predicted blood-brain barrier permeability, did not exert any significant cytotoxic effects in immature cortical neurons up to 50 μM and showed neuroprotective properties at micromolar concentration against toxic insult induced by glutamate.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc18016425
- 003
- CZ-PrNML
- 005
- 20221024104448.0
- 007
- ta
- 008
- 180515s2017 fr f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.ejmech.2017.07.058 $2 doi
- 035 __
- $a (PubMed)28810189
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a fr
- 100 1_
- $a De Simone, Angela $u Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
- 245 10
- $a Hydroxy-substituted trans-cinnamoyl derivatives as multifunctional tools in the context of Alzheimer's disease / $c A. De Simone, M. Bartolini, A. Baschieri, KYP. Apperley, HH. Chen, M. Guardigni, S. Montanari, T. Kobrlova, O. Soukup, L. Valgimigli, V. Andrisano, JW. Keillor, M. Basso, A. Milelli,
- 520 9_
- $a Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (Aβ), glycogen synthase kinase 3β (GSK-3β) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments. We designed compound 3 which demonstrated the ability to inhibit both GSK-3β (IC50 = 24.36 ± 0.01 μM) and Aβ42 self-aggregation (IC50 = 9.0 ± 1.4 μM), to chelate copper (II) and to act as exceptionally strong radical scavenger (kinh = 6.8 ± 0.5 · 105 M-1s-1) even in phosphate buffer at pH 7.4 (kinh = 3.2 ± 0.5 · 105 M-1s-1). Importantly, compound 3 showed high-predicted blood-brain barrier permeability, did not exert any significant cytotoxic effects in immature cortical neurons up to 50 μM and showed neuroprotective properties at micromolar concentration against toxic insult induced by glutamate.
- 650 _2
- $a Alzheimerova nemoc $x farmakoterapie $x metabolismus $7 D000544
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a cinnamáty $x chemická syntéza $x chemie $x farmakologie $7 D002934
- 650 _2
- $a vztah mezi dávkou a účinkem léčiva $7 D004305
- 650 _2
- $a scavengery volných radikálů $x chemická syntéza $x chemie $x farmakologie $7 D016166
- 650 _2
- $a GSK3B $x antagonisté a inhibitory $x metabolismus $7 D000071679
- 650 _2
- $a molekulární struktura $7 D015394
- 650 _2
- $a stereoizomerie $7 D013237
- 650 _2
- $a vztahy mezi strukturou a aktivitou $7 D013329
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Bartolini, Manuela $u Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
- 700 1_
- $a Baschieri, Andrea $u Department of Chemistry "G. Ciamician", Alma Mater Studiorum-University of Bologna, Via S. Giacomo 11, 40126 Bologna, Italy.
- 700 1_
- $a Apperley, Kim Y P $u Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON, K1N 6N5, Canada.
- 700 1_
- $a Chen, Huan Huan $u Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
- 700 1_
- $a Guardigni, Melissa $u Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
- 700 1_
- $a Montanari, Serena $u Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
- 700 1_
- $a Kobrlová, Tereza, $u Biomedical Research Center, University Hospital, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. $d 1991- $7 xx0277928
- 700 1_
- $a Soukup, Ondrej $u Biomedical Research Center, University Hospital, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
- 700 1_
- $a Valgimigli, Luca $u Department of Chemistry "G. Ciamician", Alma Mater Studiorum-University of Bologna, Via S. Giacomo 11, 40126 Bologna, Italy.
- 700 1_
- $a Andrisano, Vincenza $u Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
- 700 1_
- $a Keillor, Jeffrey W $u Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, ON, K1N 6N5, Canada.
- 700 1_
- $a Basso, Manuela $u Laboratory of Transcriptional Neurobiology, Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123 Trento, Italy.
- 700 1_
- $a Milelli, Andrea $u Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy. Electronic address: andrea.milelli3@unibo.it.
- 773 0_
- $w MED00001628 $t European journal of medicinal chemistry $x 1768-3254 $g Roč. 139, č. - (2017), s. 378-389
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/28810189 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20180515 $b ABA008
- 991 __
- $a 20221024104446 $b ABA008
- 999 __
- $a ok $b bmc $g 1300049 $s 1013265
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2017 $b 139 $c - $d 378-389 $e 20170725 $i 1768-3254 $m European journal of medicinal chemistry $n Eur J Med Chem $x MED00001628
- LZP __
- $a Pubmed-20180515
