Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Design, synthesis and biological assessment of new 1-benzyl-4-((4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium derivatives (BOPs) as potential dual inhibitors of acetylcholinesterase and butyrylcholinesterase.

ABSTRACT: Alzheimer's disease (AD), is among the most growing neurodegenerative diseases, which is mainly caused by the acetylcholine neurotransmitter loss in the hippocampus and cortex. Emerging of the dual Acetylcholinesterase (AChE)/Butyrylcholinesterase (BuChE) inhibitors has increased for treating Alzheimer disease. In this study, we would like to report the design and synthesis of a new sequence of 1-benzyl-4-((4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium derivatives (BOPs) assessed as BuChE and AChE inhibitors. Ellman's approach was used for the evaluation of AChE and BuChE inhibitory activities. Moreover, docking research was conducted to predict the action mechanism. Among all synthesized compounds, 1-(3-bromobenzyl)-3-((4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium bromide (BOP-1) was found to be the most active compound with dual activity for inhibition of AChE (IC₅₀ = 5.90 ± 0.07μM), and BuChE (IC₅₀ = 6.76 ± 0.04μM) and 1-(4-chlorobenzyl)-3-((6,7-dimethoxy-4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium chloride (BOP-8) showed the highest AChE inhibitory activity (IC₅₀s = 1.11 ± 0.09 μM). The synthesized compounds BOP-1 and BOP-8 could be proposed as valuable lead compounds for further drug discovery development against AD.

SUBMITTER: Zarei S

PROVIDER: S-EPMC8045006 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

5,6-Dimethoxybenzofuran-3-one derivatives: a novel series of dual Acetylcholinesterase/Butyrylcholinesterase inhibitors bearing benzyl pyridinium moiety.

Project description:Several studies have been focused on design and synthesis of multi-target anti Alzheimer compounds. Utilizing of the dual Acetylcholinesterase/Butyrylcholinesterase inhibitors has gained more interest to treat the Alzheimer's disease. As a part of a research program to find a novel drug for treating Alzheimer disease, we have previously reported 6-alkoxybenzofuranone derivatives as potent acetylcholinesterase inhibitors. In continuation of our work, we would like to report the synthesis of 5,6-dimethoxy benzofuranone derivatives bearing a benzyl pyridinium moiety as dual Acetylcholinesterase/Butyrylcholinesterase inhibitors.The synthesis of target compounds was carried out using a conventional method. Bayer-Villiger oxidation of 3,4-dimethoxybenzaldehyde furnished 3,4-dimethoxyphenol. The reaction of 3,4-dimethoxyphenol with chloroacetonitrile followed by treatment with HCl solution and then ring closure yielded the 5,6-dimethoxy benzofuranone. Condensation of the later compound with pyridine-4-carboxaldehyde and subsequent reaction with different benzyl halides afforded target compounds. The biological activity was measured using standard Ellman's method. Docking studies were performed to get better insight into interaction of compounds with receptor.The in vitro anti acetylcholinesterase/butyrylcholinesterase activity of compounds revealed that, all of the target compounds have good inhibitory activity against both Acetylcholinesterase/Butyrylcholinesterase enzymes in which compound 5b (IC50 = 52 ± 6.38nM) was the most active compound against acetylcholinesterase. The same binding mode and interactions were observed for the reference drug donepezil and compound 5b in docking study.In this study, we presented a new series of benzofuranone-based derivatives having pyridinium moiety as potent dual acting Acetylcholinesterase/Butyrylcholinesterase inhibitors.

| S-EPMC3599263 | biostudies-literature

Synthesis and biological evaluation of lycorine derivatives as dual inhibitors of human acetylcholinesterase and butyrylcholinesterase.

Project description:UnlabelledBackgroundAlzheimer's disease (AD) is a neurologically degenerative disorder that affects more than 20 million people worldwide. The selective butyrylcholinesterase (BChE) inhibitors and bivalent cholinesterase (ChE) inhibitors represent new treatments for AD.FindingsA series of lycorine derivatives (1-10) were synthesized and evaluated for anti-cholinesterase activity. Result showed that the novel compound 2-O-tert-butyldimethylsilyl-1-O-(methylthio)methyllycorine (7) was a dual inhibitor of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) with IC50 values of 11.40 ± 0.66 ?M and 4.17 ± 0.29 ?M, respectively. The structure-activity relationships indicated that (i) the 1-O-(methylthio)methyl substituent in lycorine was better than the 1-O-acetyl group for the inhibition of cholinesterase; (ii) the acylated or etherified derivatives of lycorine and lycorin-2-one were more potent against hBChE than hAChE; and (iii) the oxidation of lycorine at C-2 decreases the activity.ConclusionAcylated or etherified derivatives of lycorine are potential dual inhibitors of hBChE and hAChE. Hence, further study on the modification of lycorine for ChE inhibition is necessary.

| S-EPMC3782361 | biostudies-literature

1-[(Methyl-sulfon-yl)-oxy]pyridin-1-ium methane-sulfonate.

Project description:The title mol-ecular salt, C6H8NO3S+·CH3O3S-, consists of a cationic sulfonated pyridine N-oxide moiety and a methane-sulfonate anion. An N-O bond length of 1.4004 (15) Å is observed in the cation. In the crystal, weak C-H⋯O inter-actions link the components into a three-dimensional network.

| S-EPMC9462295 | biostudies-literature

Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase.

Project description:Alzheimer's disease (AD), the most common form of dementia in adults, is a progressive neurodegenerative disorder of the brain characterized by loss of memory and steady deterioration of cognition. Here, a series of symmetrical molecules containing biphenyl/bibenzyl scaffolds (12-36) were designed, synthesized, and evaluated for their ability to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A biological evaluation showed that most of these biphenyl derivatives were potent AChE and BuChE inhibitors. Among them, compound 15 displayed the greatest ability to inhibit BuChE (IC50 = 0.74 µM) and was also a good AChE inhibitor (IC50 = 1.18 µM). Compound 19 was not only a potent AChE inhibitor (IC50 = 0.096 µM), but also a mild BuChE inhibitor (IC50 =1.25 µM). Overall, these results suggested that compound 19 may be a promising agent in the treatment of AD.

| S-EPMC6155837 | biostudies-literature

4-[2-(Pyridin-1-ium-4-yl)eth-yl]pyridin-1-ium bis-(2,6-di-nitro-benzoate).

Project description:The asymmetric unit of the title salt, C12H14N2 (2+)·2C7H3N2O6 (-), comprises half a 4-[2-(pyridin-1-ium-4-yl)eth-yl]pyridin-1-ium dication, being disposed about a centre of inversion, and a 2,6-di-nitro-benzoate anion, in a general position. In the anion, the carboxyl-ate group is inclined to the benzene ring [dihedral angle = 85.45?(9)°], whereas near-coplanar and twisted arrangements are found for the nitro groups [O-N-C-C torsion angles = 179.80?(14) and 20.2?(2)°]. In the crystal, three-component aggregates sustained by charge-assisted N(+)-H?O(-) hydrogen bonds are found and these are consolidated into a three-dimensional architecture by C-H?O and ?-? [inter-centroid distances = 3.6796?(14) and 3.7064?(14)?Å] inter-actions.

| S-EPMC3884282 | biostudies-literature

{S-Benzyl 3-[(6-methyl-pyridin-2-yl)-methyl-idene]dithio-carbazato}nickel(II) monohydrate.

Project description:The structure of the title compound, [Ni(C(15)H(14)N(3)S(2))(2)]·H(2)O, has one mol-ecule in the asymmetric unit, along with a solvent water mol-ecule. The two different Schiff base moieties coordinate to the central Ni(II) ion as tridentate N,N',S-chelating ligands, creating a six-coordinate distorted octa-hedral environment [the smallest angle being 77.43?(7)° and the widest angle being 169.99?(7)°]. The mean planes of the two ligands are nearly orthogonal to each other with an angle of 89.53?(6)°. The packing of the complex is supported by O-H?N and O-H?S hydrogen bonding between the solvent water mol-ecule and the uncoordinated N and S atoms of neighbouring ligands.

| S-EPMC3297266 | biostudies-literature

Bis{S-benzyl 3-[(6-methyl-pyridin-2-yl)methyl-idene]dithio-carbazato}nickel(II).

Project description:The asymmetric unit of the title compound, [Ni(C(15)H(14)N(3)S(2))(2)], consists of two independent mol-ecules with similar configurations. Each Ni(2+) cation is coordinated in a cis-mode by two tridentate N,N',S-chelating Schiff base ligands, creating a distorted octa-hedron [the smallest angle being 77.57?(7)° and the widest being 168.97?(7)° for one mol-ecule, and 78.04?(7) and 167.55?(7)° for the second mol-ecule]. The dihedral angle between the mean coordination planes of the two ligands is 86.76?(7)° for one and 89.99?(7)° for the second mol-ecule. ?-? inter-actions between neighbouring pyridine rings with plane-to-plane distances of 3.540?(1) and 3.704?(1)?Å are observed.

| S-EPMC3344386 | biostudies-literature

1,3-Bis(6-methyl-pyridin-2-yl)-1H-imidazol-3-ium hexa-fluoro-phosphate.

Project description:In the title salt, C17H19N4 (+)·PF6 (-), the two pyridine rings of the cation are inclined to one another by 15.89 (8)°, and inclined to the imidazole ring by 65.05 (10) and 64.07 (10)°. In the crystal, the cations and anions are linked via a series of C-H⋯N and C-H⋯F hydrogen bonds, forming two-dimensional networks lying parallel to (001).

| S-EPMC3629601 | biostudies-literature

Discovery of pyrrole derivatives as acetylcholinesterase-sparing butyrylcholinesterase inhibitor.

Project description:Inspired by the crucial roles of (hetero)aryl rings in cholinesterase inhibitors and the pyrrole ring in new drug discovery, we synthesized 19 pyrrole derivatives and investigated their cholinesterase inhibitory activity. As a result, compounds 3o, 3p, and 3s with a 1,3-diaryl-pyrrole skeleton showed high selectivity toward BChE over AChE with a best IC50 value of 1.71 ± 0.087 µM, which were comparable to donepezil. The pharmaceutical potential of these structures was further predicted and compounds 3o and 3p were proved to meet well with the Lipinsky's five rules. In combination of the inhibition kinetic studies with the results of molecular docking, we concluded that compound 3p inhibited BChE in a mixed competitive mode. This research has proved the potential of the 1,3-diaryl-pyrrole skeleton as a kind of selective BChE inhibitor.

| S-EPMC9763612 | biostudies-literature

Crystal structures of two stilbazole derivatives: bis-{(E)-4-[4-(di-ethyl-amino)-styr-yl]-1-methyl-pyridin-1-ium} tetra-iodido-cadmium(II) and (E)-4-[4-(di-ethyl-amino)-styr-yl]-1-methyl-pyridin-1-ium 4-meth-oxy-benzene-sulfonate monohydrate.

Project description:The title mol-ecular salts, (C18H23N2)2[CdI4], (I), and C18H23N2 +·C7H7O4S-·H2O, (II), are stilbazole, or 4-styryl-pyridine, derivatives. The cation, (E)-4-[4-(di-ethyl-amino)-styr-yl]-1-methyl-pyridin-1-ium, has a methyl group attached to pyridine ring and a diethyl amine group attached to the benzene ring. The asymmetric unit of salt (I), comprises one cationic mol-ecule and half a CdI4 dianion. The Cd atom is situated on a twofold rotation axis and has a slightly distorted tetra-hedral coordination sphere. In (II), the anion consists of a 4-meth-oxy-benzene-sulfonate and it crystallizes as a monohydrate. In both salts, the cations adopt an E configuration with respect to the C=C bond and the pyridine and benzene rings are inclined to each other by 10.7 (4)° in (I) and 4.6 (2)° in (II). In the crystals of both salts, the packing is consolidated by offset π-π stacking inter-actions involving the pyridinium and benzene rings, with centroid-centroid distances of 3.627 (4) Å in (I) and 3.614 (3) Å in (II). In the crystal of (II), a pair of 4-meth-oxy-benzene-sulfonate anions are bridged by Owater-H⋯Osulfonate hydrogen bonds, forming loops with an R 2 4(8) motif. These four-membered units are then linked to the cations by a number of C-H⋯O hydrogen bonds, forming slabs lying parallel to the ab plane.

| S-EPMC6281098 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data