-
Something wrong with this record ?
7-MEOTA-donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies
J. Korabecny, R. Dolezal, P. Cabelova, A. Horova, E. Hruba, J. Ricny, L. Sedlacek, E. Nepovimova, K. Spilovska, M. Andrs, K. Musilek, V. Opletalova, V. Sepsova, D. Ripova, K. Kuca,
European journal of medicinal chemistry.
2014 ;
82 (-) :
426-38.
Language English Country France
Document type Journal Article, Research Support, Non-U.S. Gov't
Persistent link
https://www.medvik.cz/link/bmc15014221
- MeSH
- Acetylcholinesterase metabolism MeSH
- Butyrylcholinesterase blood metabolism MeSH
- Cholinesterase Inhibitors chemical synthesis chemistry pharmacology MeSH
- Electrophorus MeSH
- Indans chemistry pharmacology MeSH
- Horses MeSH
- Quantitative Structure-Activity Relationship * MeSH
- Humans MeSH
- Models, Molecular MeSH
- Molecular Structure MeSH
- Piperidines chemistry pharmacology MeSH
- Recombinant Proteins metabolism MeSH
- Tacrine analogs & derivatives chemistry pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (EeAChE), human recombinant AChE (hAChE), equine serum butyrylcholinesterase (eqBChE) and human plasmatic BChE (hBChE). New hybrids consist of a 7-MEOTA unit, representing less toxic tacrine (THA) derivative, connected with analogues of N-benzylpiperazine moieties mimicking N-benzylpiperidine fragment from donepezil. 7-MEOTA-donepezil like compounds exerted mostly non-selective profile in inhibiting cholinesterases of different origin with IC50 ranging from micromolar to sub-micromolar concentration scale. Kinetic analysis confirmed mixed-type inhibition presuming that these inhibitors are capable to simultaneously bind peripheral anionic site (PAS) as well as catalytic anionic site (CAS) of AChE. Molecular modeling studies and QSAR studies were performed to rationalize studies from in vitro. Overall, 7-MEOTA-donepezil like derivatives can be considered as interesting candidates for Alzheimer's disease treatment.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc15014221
- 003
- CZ-PrNML
- 005
- 20150427101337.0
- 007
- ta
- 008
- 150420s2014 fr f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.ejmech.2014.05.066 $2 doi
- 035 __
- $a (PubMed)24929293
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a fr
- 100 1_
- $a Korabecny, Jan $u Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
- 245 10
- $a 7-MEOTA-donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies / $c J. Korabecny, R. Dolezal, P. Cabelova, A. Horova, E. Hruba, J. Ricny, L. Sedlacek, E. Nepovimova, K. Spilovska, M. Andrs, K. Musilek, V. Opletalova, V. Sepsova, D. Ripova, K. Kuca,
- 520 9_
- $a A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (EeAChE), human recombinant AChE (hAChE), equine serum butyrylcholinesterase (eqBChE) and human plasmatic BChE (hBChE). New hybrids consist of a 7-MEOTA unit, representing less toxic tacrine (THA) derivative, connected with analogues of N-benzylpiperazine moieties mimicking N-benzylpiperidine fragment from donepezil. 7-MEOTA-donepezil like compounds exerted mostly non-selective profile in inhibiting cholinesterases of different origin with IC50 ranging from micromolar to sub-micromolar concentration scale. Kinetic analysis confirmed mixed-type inhibition presuming that these inhibitors are capable to simultaneously bind peripheral anionic site (PAS) as well as catalytic anionic site (CAS) of AChE. Molecular modeling studies and QSAR studies were performed to rationalize studies from in vitro. Overall, 7-MEOTA-donepezil like derivatives can be considered as interesting candidates for Alzheimer's disease treatment.
- 650 _2
- $a acetylcholinesterasa $x metabolismus $7 D000110
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a butyrylcholinesterasa $x krev $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 Electrophorus $7 D004593
- 650 _2
- $a koně $7 D006736
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a indany $x chemie $x farmakologie $7 D007189
- 650 _2
- $a molekulární modely $7 D008958
- 650 _2
- $a molekulární struktura $7 D015394
- 650 _2
- $a piperidiny $x chemie $x farmakologie $7 D010880
- 650 12
- $a kvantitativní vztahy mezi strukturou a aktivitou $7 D021281
- 650 _2
- $a rekombinantní proteiny $x metabolismus $7 D011994
- 650 _2
- $a takrin $x analogy a deriváty $x chemie $x farmakologie $7 D013619
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Dolezal, Rafael $u Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
- 700 1_
- $a Cabelova, Pavla $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 Horova, Anna $u Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
- 700 1_
- $a Hruba, Eva $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 Ricny, Jan $u Laboratory of Biochemistry and Brain Pathophysiology and AD Center, Prague Psychiatric Center, Ustavni 91, 181 03 Prague 8, Czech Republic.
- 700 1_
- $a Sedlacek, Lukas $u Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Vinicna 7, 128 43 Prague, Czech Republic.
- 700 1_
- $a Nepovimova, Eugenie $u Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
- 700 1_
- $a Spilovska, Katarina $u Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
- 700 1_
- $a Andrs, Martin $u Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic. $7 gn_A_00006738
- 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 Opletalova, Veronika $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 Sepsova, Vendula $u Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
- 700 1_
- $a Ripova, Daniela $u Laboratory of Biochemistry and Brain Pathophysiology and AD Center, Prague Psychiatric Center, Ustavni 91, 181 03 Prague 8, Czech Republic.
- 700 1_
- $a Kuca, Kamil $u Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic; Centre for Advanced Studies, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03 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. 82, č. - (2014), s. 426-38
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/24929293 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20150420 $b ABA008
- 991 __
- $a 20150427101641 $b ABA008
- 999 __
- $a ok $b bmc $g 1071802 $s 897099
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2014 $b 82 $c - $d 426-38 $i 1768-3254 $m European journal of medicinal chemistry $n Eur J Med Chem $x MED00001628
- LZP __
- $a Pubmed-20150420
