Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and Biological Evaluation of Thiazole-Based Derivatives as Potential Acetylcholinesterase Inhibitors.

ABSTRACT: Nineteen new thiazole-based derivatives were synthesized and their structures characterized with analytical and spectral data. The in vitro assessment of their acetylcholinesterase (AChE) inhibitory activity revealed that compounds 10 and 16 produced potent AChE inhibitory activities with IC₅₀ values of 103.24 and 108.94 nM, respectively. Compounds 13, 17, 18, 21, 23, 31, and 33 displayed moderate activity with 25-50% relative potency compared to the known potent AChE inhibitor donepezil. Molecular docking studies of the active compounds docked within the active site cavity of AChE showed a binding orientation similar to that of donepezil, with good predicted binding affinities. These compounds could therefore be considered as potential lead compounds for the development of new and potentially improved AChE inhibitors.

SUBMITTER: Hemaida AY

PROVIDER: S-EPMC8320107 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Synthesis and biological evaluation of thiophene derivatives as acetylcholinesterase inhibitors.

Project description:A series of new thiophene derivatives has been synthesized using the Gewald protocol. The acetylcholinesterase inhibition activity was assayed according to Ellman's method using donepezil as reference. Some of the compounds were found to be more potent inhibitors than the reference. 2-(2-(4-(4-Methoxyphenyl)piperazin-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (IIId) showed 60% inhibition, compared to only 40% inhibition by donepezil.

| S-EPMC6268334 | biostudies-literature

Design, synthesis and biological evaluation of novel thiazole-naphthalene derivatives as potential anticancer agents and tubulin polymerisation inhibitors.

Project description:A novel series of thiazole-naphthalene derivatives as tubulin polymerisation inhibitors were designed, synthesised, and evaluated for the anti-proliferative activities. The majority of the tested compounds exhibited moderate to potent antiproliferative activity on the MCF-7 and A549 cancer cell lines. Among them, compound 5b was found to be the most active compound with IC50 values of 0.48 ± 0.03 and 0.97 ± 0.13 μM. Moreover, mechanistic studies revealed that 5b significantly inhibited tubulin polymerisation with an IC50 value of 3.3 µM, as compared to the standard drug colchicine (IC50 = 9.1 μM). Further cellular mechanism studies elucidated that 5b arrested the cell cycle at G2/M phase and induced apoptosis in MCF-7 cancer cells. Molecular modelling study indicated that 5b binds well to the colchicine binding site of tubulin. In summary, these results suggest that 5b represents a promising tubulin polymerisation inhibitor worthy of further investigation as potential anticancer agents.

| S-EPMC8317958 | biostudies-literature

Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel Isatin-Thiazole Derivatives as ?-Glucosidase Inhibitors.

Project description:A series of novel isatin-thiazole derivatives were synthesized and screened for their in vitro ?-glucosidase inhibitory activity. These compounds displayed a varying degree of ?-glucosidase inhibitory activity with IC50 ranging from 5.36 ± 0.13 to 35.76 ± 0.31 ?m as compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 ?m). Among the series, compound 6p bearing a hydroxyl group at the 4-position of the right phenyl and 2-fluorobenzyl substituent at the N1-positions of the 5-methylisatin displayed the highest inhibitory activity with an IC50 value of 5.36 ± 0.13 ?m. Molecular docking studies revealed the existence of hydrophobic interaction, CH-? interaction, arene-anion interaction, arene-cation interaction, and hydrogen bond between these compounds and ?-glucosidase enzyme.

| S-EPMC6154535 | 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

Design, Synthesis and Biological Evaluation of New Imidazo[2,1-b]Thiazole Derivatives as Selective COX-2 Inhibitors.

Project description:A new series of imidazo[2,1-b]thiazole analogs containing a methyl sulfonyl COX-2 pharmacophore was synthesized and evaluated for their COX-2 inhibitory activity. According to in-vitro COX-1/COX-2 inhibition data, all compounds (6a-g) were selective inhibitors of COX-2 isoenzyme with IC50 values in the highly potent 0.08-0.16 µM range. These results indicated that both potency and selectivity of COX-2 inhibitory activity were affected by the type and size of amine on C-5 of imidazo[2,1-b]thiazole ring. Our data identified N,N-dimethyl-1-(6-(4-(methylsulfonyl)phenyl)imidazo[2,1-b]thiazol-5-yl)methanamine (6a) as a potent and selective COX-2 inhibitor (IC50 COX-1 >100 µM; IC50 COX-2 = 0.08 µM; selectivity index = 313.7). Our results indicated that both potency and selectivity of COX-2 inhibitory activity were affected by the type and size of amine on C-5 of imidazo[2,1-b]thiazole ring.

| S-EPMC6269562 | biostudies-literature

Synthesis of new indole derivatives structurally related to donepezil and their biological evaluation as acetylcholinesterase inhibitors.

Project description:New series of indole derivatives analogous to donepezil, a well known anti-Alzheimer and acetylcholinesterase inhibitor drug, was synthesized. A full chemical characterization of the new compounds is provided. Biological evaluation of the new compounds as acetylcholinesterase inhibitors was performed. Most of the compounds were found to have potent acetylcholinesterase inhibitor activity compared to donepezil as standard. The compound 1-(2-(4-(2-fluorobenzyl) piperazin-1-yl)acetyl)indoline-2,3-dione (IIId) was found to be the most potent.

| S-EPMC6268345 | biostudies-literature

Arylaminopropanone Derivatives as Potential Cholinesterase Inhibitors: Synthesis, Docking Study and Biological Evaluation.

Project description:Neurodegenerative diseases in which the decrease of the acetylcholine is observed are growing worldwide. In the present study, a series of new arylaminopropanone derivatives with N-phenylcarbamate moiety (1-16) were prepared as potential acetylcholinesterase and butyrylcholinesterase inhibitors. In vitro enzyme assays were performed; the results are expressed as a percentage of inhibition and the IC50 values. The inhibitory activities were compared with reference drugs galantamine and rivastigmine showing piperidine derivatives (1-3) as the most potent. A possible mechanism of action for these compounds was determined from a molecular modelling study by using combined techniques of docking, molecular dynamics simulations and quantum mechanics calculations.

| S-EPMC7180927 | biostudies-literature

Virtual screening and biological evaluation of piperazine derivatives as human acetylcholinesterase inhibitors.

Project description:The piperazine derivatives have been shown to inhibit human acetylcholinesterase. Virtual screening by molecular docking of piperazine derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K), 4-(4-methyl)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S1), and 4-(4-chloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S3) has been shown to bind at peripheral anionic site and catalytic sites, whereas 4-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S4) and 4-(2,5-dichloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S7) do not bind either to peripheral anionic site or catalytic site with hydrogen bond. All the derivatives have differed in number of H-bonds and hydrophobic interactions. The peripheral anionic site interacting molecules have proven to be potential therapeutics in inhibiting amyloid peptides aggregation in Alzheimer's disease. All the piperazine derivatives follow Lipinski's rule of five. Among all the derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K) was found to have the lowest TPSA value.

| S-EPMC3830860 | biostudies-literature

Stereoselective synthesis, X-ray analysis, computational studies and biological evaluation of new thiazole derivatives as potential anticancer agents.

Project description:BACKGROUND:The synthesis of new thiazole derivatives is very important because of their diverse biological activities. Also , many drugs containing thiazole ring in their skeletons are available in the market such as Abafungin, Acotiamide, Alagebrium, Amiphenazole, Brecanavir, Carumonam, Cefepime, and Cefmatilen. RESULTS:Ethyl cyanoacetate reacted with phenylisothiocyanate, chloroacetone, in two different basic mediums to afford the thiazole derivative 6, which reacted with dimethylformamide- dimethyl acetal in the presence of DMF to afford the unexpected thiazole derivative 11. The structures of the thiazoles 6 and 11 were optimized using B3LYP/6-31G(d,p) method. The experimentally and theoretically geometric parameters agreed very well. Also, the natural charges at the different atomic sites were predicted. HOMO and LUMO demands were discussed. The anticancer activity of the prepared compounds was evaluated and showed moderate activity. CONCLUSIONS:Synthesis of novel thiazole derivatives was done. The structure was established using X-ray and spectral analysis. Optimized molecular structures at the B3LYP/6-31G(d,p) level were investigated. Thiazole derivative 11 has more electropositive S-atom than thiazole 6. The HOMO-LUMO energy gap is lower in the former compared to the latter. The synthesized compounds showed moderate anticancer activity.

| S-EPMC5945573 | biostudies-literature

Synthesis and Biological Activity Evaluation of 2-Cyanopyrrole Derivatives as Potential Tyrosinase Inhibitors.

Project description:In order to find potential inhibitors of tyrosinase, two series of pyrrole derivatives A (1-17) and B (1-8) were synthesized and screened for their inhibitory activities on tyrosinase. Most of the 2-cyanopyrrole derivatives exhibited effective inhibitory activities. In particular, A12 exhibited the strongest inhibitory activities, with the IC50 values of 0.97 μM, which is ∼30 times stronger than the reference inhibitor kojic acid (IC50: 28.72 μM). The inhibitory mechanism analysis results revealed that A12 was a reversible and mixed-type inhibitor. Molecular docking experiments clarified the interaction between A12 with tyrosinase. Furthermore, A12 (100 μM) presented effective inhibitory effect on tyrosinase in B16 melanoma cells with inhibition of 33.48%, which was equivalent to that of Kojic acid (39.81%). Accordingly, compound A12 may serve as the lead structure for the further design of potent tyrosinase inhibitors. Molecular docking studies confirmed the interaction between the compound and tyrosinase.

| S-EPMC9247258 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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