-
Something wrong with this record ?
Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer's disease
R. Peřinová, N. Maafi, J. Korábečný, E. Kohelová, A. De Simone, A. Al Mamun, D. Hulcová, J. Marková, T. Kučera, D. Jun, M. Šafratová, J. Maříková, V. Andrisano, J. Jenčo, J. Kuneš, A. Martinez, L. Nováková, L. Cahlíková
Bioorganic chemistry.
2020 ;
100 (-) :
103928.
[pub] 20200517
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Persistent link
https://www.medvik.cz/link/bmc21012401
- MeSH
- Acetylcholinesterase chemistry metabolism MeSH
- Amaryllidaceae Alkaloids chemistry metabolism therapeutic use MeSH
- Alzheimer Disease drug therapy pathology MeSH
- Amaryllidaceae chemistry metabolism MeSH
- Butyrylcholinesterase chemistry metabolism MeSH
- Cholinesterase Inhibitors chemical synthesis metabolism therapeutic use MeSH
- Esters chemistry MeSH
- Phenanthridines chemistry metabolism therapeutic use MeSH
- Blood-Brain Barrier drug effects metabolism MeSH
- Kinetics MeSH
- Humans MeSH
- Molecular Docking Simulation MeSH
- Binding Sites MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
A novel series of aromatic esters (1a-1m) related to the Amaryllidaceae alkaloid (AA) haemanthamine were designed, synthesized and tested in vitro with particular emphasis on the treatment of neurodegenerative diseases. Some of the synthesized compounds revealed promising acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory profile. Significant human AChE (hAChE) inhibition was demonstrated by 11-O-(3-nitrobenzoyl)haemanthamine (1j) with IC50value of 4.0 ± 0.3 µM. The strongest human BuChE (hBuChE) inhibition generated 1-O-(2-methoxybenzoyl)haemanthamine (1g) with IC50 value 3.3 ± 0.4 µM. Moreover, 11-O-(2-chlorbenzoyl)haemanthamine (1m) was able to inhibit both enzymes in dose-dependent manner. The mode of hAChE and hBuChE inhibition was minutely inspected using enzyme kinetic analysis in tandem with in silico experiments, the latter elucidating crucial interaction in 1j-, 1m-hAChE and 1g-, 1m-hBuChE complexes. The blood-brain barrier (BBB) permeability was investigated applying the parallel artificial membrane permeation assay (PAMPA) to predict the CNS availability of the compounds.
Centro de Investigaciones Biológicas CSIC Avenida Ramiro de Maeztu 9 28040 Madrid Spain
Department for Life Quality Studies University of Bologna Corso D'Augusto 237 47921 Rimini Italy
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc21012401
- 003
- CZ-PrNML
- 005
- 20210507101709.0
- 007
- ta
- 008
- 210420s2020 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.bioorg.2020.103928 $2 doi
- 035 __
- $a (PubMed)32450384
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Peřinová, Rozálie $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 245 10
- $a Functionalized aromatic esters of the Amaryllidaceae alkaloid haemanthamine and their in vitro and in silico biological activity connected to Alzheimer's disease / $c R. Peřinová, N. Maafi, J. Korábečný, E. Kohelová, A. De Simone, A. Al Mamun, D. Hulcová, J. Marková, T. Kučera, D. Jun, M. Šafratová, J. Maříková, V. Andrisano, J. Jenčo, J. Kuneš, A. Martinez, L. Nováková, L. Cahlíková
- 520 9_
- $a A novel series of aromatic esters (1a-1m) related to the Amaryllidaceae alkaloid (AA) haemanthamine were designed, synthesized and tested in vitro with particular emphasis on the treatment of neurodegenerative diseases. Some of the synthesized compounds revealed promising acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory profile. Significant human AChE (hAChE) inhibition was demonstrated by 11-O-(3-nitrobenzoyl)haemanthamine (1j) with IC50value of 4.0 ± 0.3 µM. The strongest human BuChE (hBuChE) inhibition generated 1-O-(2-methoxybenzoyl)haemanthamine (1g) with IC50 value 3.3 ± 0.4 µM. Moreover, 11-O-(2-chlorbenzoyl)haemanthamine (1m) was able to inhibit both enzymes in dose-dependent manner. The mode of hAChE and hBuChE inhibition was minutely inspected using enzyme kinetic analysis in tandem with in silico experiments, the latter elucidating crucial interaction in 1j-, 1m-hAChE and 1g-, 1m-hBuChE complexes. The blood-brain barrier (BBB) permeability was investigated applying the parallel artificial membrane permeation assay (PAMPA) to predict the CNS availability of the compounds.
- 650 _2
- $a acetylcholinesterasa $x chemie $x metabolismus $7 D000110
- 650 _2
- $a Alzheimerova nemoc $x farmakoterapie $x patologie $7 D000544
- 650 _2
- $a Amaryllidaceae $x chemie $x metabolismus $7 D000070378
- 650 _2
- $a alkaloidy amarylkovitých $x chemie $x metabolismus $x terapeutické užití $7 D047151
- 650 _2
- $a vazebná místa $7 D001665
- 650 _2
- $a hematoencefalická bariéra $x účinky léků $x metabolismus $7 D001812
- 650 _2
- $a butyrylcholinesterasa $x chemie $x metabolismus $7 D002091
- 650 _2
- $a cholinesterasové inhibitory $x chemická syntéza $x metabolismus $x terapeutické užití $7 D002800
- 650 _2
- $a estery $x chemie $7 D004952
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a kinetika $7 D007700
- 650 _2
- $a simulace molekulového dockingu $7 D062105
- 650 _2
- $a fenantridiny $x chemie $x metabolismus $x terapeutické užití $7 D010617
- 650 _2
- $a vztahy mezi strukturou a aktivitou $7 D013329
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Maafi, Negar $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Korábečný, Jan $u Department of Toxicology and Military Pharmacy, University of Defence, Trebesska 1575, 500 05 Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Kohelová, Eliška $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a De Simone, Angela $u Department for Life Quality Studies, University of Bologna, Corso D'Augusto 237, 47921 Rimini, Italy
- 700 1_
- $a Al Mamun, Abdullah $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Hulcová, Daniela $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic; Department of Pharmacognosy, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Marková, Jana $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Kučera, Tomáš $u Department of Toxicology and Military Pharmacy, University of Defence, Trebesska 1575, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Jun, Daniel $u Department of Toxicology and Military Pharmacy, University of Defence, Trebesska 1575, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Šafratová, Marcela $u Department of Pharmacognosy, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Maříková, Jana $u Department of Bioorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Andrisano, Vincenza $u Department for Life Quality Studies, University of Bologna, Corso D'Augusto 237, 47921 Rimini, Italy
- 700 1_
- $a Jenčo, Jaroslav $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Kuneš, Jiří $u Department of Bioorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Martinez, Ana $u Centro de Investigaciones Biológicas-CSIC, Avenida Ramiro de Maeztu, 9, 28040 Madrid, Spain
- 700 1_
- $a Nováková, Lucie $u Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
- 700 1_
- $a Cahlíková, Lucie $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. Electronic address: cahlikova@faf.cuni.cz
- 773 0_
- $w MED00000771 $t Bioorganic chemistry $x 1090-2120 $g Roč. 100, č. - (2020), s. 103928
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/32450384 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20210420 $b ABA008
- 991 __
- $a 20210507101709 $b ABA008
- 999 __
- $a ok $b bmc $g 1650715 $s 1132780
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2020 $b 100 $c - $d 103928 $e 20200517 $i 1090-2120 $m Bioorganic chemistry $n Bioorg Chem $x MED00000771
- LZP __
- $a Pubmed-20210420
