Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors.

ABSTRACT: A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC₅₀ values in the range of 6.31 to 49.89 μM compared to standard drug acarbose (IC₅₀ = 750.0 ± 10.0 μM). Enzyme kinetic studies on 9c, 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor.

SUBMITTER: Nasli Esfahani A

PROVIDER: S-EPMC8436581 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Design and synthesis of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-2H-1,2,3-triazole derivatives as colchicine binding site inhibitors.

Project description:A series of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-2H-1,2,3-triazol derivatives were designed as potential microtubule targeting agents. The regioselective alkylation of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-2H-1,2,3-triazole was predicted by computations and confirmed by an unambiguous synthetic route. The antiproliferative activity of the synthesized compounds was tested in vitro using three human cancer cell lines and some compounds exhibited significant antiproliferative activity, which suggested the reasonability of introduction of the 1,2,3-triazole fragment. Among them, compound 7p showed highest activity with the IC50 values at nanomolar level towards all three cell lines, which were comparable to the positive control, CA-4. Tubulin polymerization assay, immunofluorescence studies, cell cycle analysis and competitive tubulin-binding assay strongly proved that 7p is a colchicine binding site inhibitor of tubulin. Thus, 7p was identified as a promising drug candidate for further development of colchicine binding site inhibitors.

| S-EPMC5719359 | biostudies-literature

Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents.

Project description:A novel series of substituted 4,6-dimethyl-2-oxo-1-(thiazol-2-ylamino)-1,2-dihydropyridine-3-carbonitrile derivatives 6, 9, 13, 15, and 17 was synthesized in a good to excellent yield from the reaction of 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)thiourea with 2-oxo-N'-arylpropanehydrazonoyl chloride, chloroacetone, α-bromoketones, ethyl chloroacetate, and 2,3-dichloroquinoxaline, respectively. The potential DNA gyrase inhibitory activity was examined using in silico molecular docking simulation. The novel thiazoles exhibit dock score values between - 6.4 and - 9.2 kcal/mol and they were screened for their antimicrobial activities. Compound 13a shown good antibacterial activities with MIC ranged from 93.7-46.9 μg/mL, in addition, it shown good antifungal activities with MIC ranged from 7.8 and 5.8 μg/mL.

| S-EPMC8041837 | biostudies-literature

Design, synthesis, and in silico studies of quinoline-based-benzo[d]imidazole bearing different acetamide derivatives as potent α-glucosidase inhibitors.

Project description:In this study, 18 novel quinoline-based-benzo[d]imidazole derivatives were synthesized and screened for their α-glucosidase inhibitory potential. All compounds in the series except 9q showed a significant α-glucosidase inhibition with IC50 values in the range of 3.2 ± 0.3-185.0 ± 0.3 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). A kinetic study indicated that compound 9d as the most potent derivative against α-glucosidase was a competitive type inhibitor. Furthermore, the molecular docking study revealed the effective binding interactions of 9d with the active site of the α-glucosidase enzyme. The results indicate that the designed compounds have the potential to be further studied as new anti-diabetic agents.

| S-EPMC9386204 | biostudies-literature

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors.

Project description:In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a-n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with Ki = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔHm°) and entropy (ΔSm°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results.

| S-EPMC9125976 | biostudies-literature

Indole-carbohydrazide linked phenoxy-1,2,3-triazole-N-phenylacetamide derivatives as potent α-glucosidase inhibitors: design, synthesis, in vitro α-glucosidase inhibition, and computational studies.

Project description:BackgroundA new series of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide hybrids 11a-o was designed based on molecular hybridization of the active pharmacophores of the potent α-glucosidase inhibitors. These compounds were synthesized and evaluated against α-glucosidase.MethodsThe 15 various derivatives of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide scaffold were synthesized, purified, and fully characterized. These derivatives were evaluated against yeast α-glucosidase in vitro and in silico. ADMET properties of the most potent compounds were also predicted.ResultsAll new derivatives 11a-o (IC50 values = 6.31 ± 0.03-49.89 ± 0.09 µM) are excellent α-glucosidase inhibitors in comparison to acarbose (IC50 value = 750.0 ± 10.0 µM) that was used as a positive control. Representatively, (E)-2-(4-((4-((2-(1H-indole-2-carbonyl)hydrazono)methyl) phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(4-methoxyphenyl)acetamide 11d with IC50 = 6.31 µM against MCF-7 cells, was 118.8-times more potent than acarbose. This compound is an uncompetitive inhibitor against α-glucosidase and showed the lowest binding energy at the active site of this enzyme in comparison to other potent compounds. Furthermore, computational calculations predicted that compound 11d can be an orally active compound.ConclusionAccording to obtained data, compound 11d can be a valuable lead compound for further structural development and assessments to obtain effective and potent new α-glucosidase inhibitors.

| S-EPMC10268488 | biostudies-literature

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

Project description:A series of novel isatin-thiazole derivatives were synthesized and screened for their in vitro α-glucosidase inhibitory activity. These compounds displayed a varying degree of α-glucosidase inhibitory activity with IC50 ranging from 5.36 ± 0.13 to 35.76 ± 0.31 μm as compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μm). 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 μm. Molecular docking studies revealed the existence of hydrophobic interaction, CH-π interaction, arene-anion interaction, arene-cation interaction, and hydrogen bond between these compounds and α-glucosidase enzyme.

| S-EPMC6154535 | biostudies-literature

Quinazolinone-1,2,3-triazole-acetamide conjugates as potent α-glucosidase inhibitors: synthesis, enzyme inhibition, kinetic analysis, and molecular docking study.

Project description:In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results obtained from the in vitro screening indicated that all analogs exhibited significant inhibitory activity against α-glucosidase (IC50 values ranging from 4.8-140.2 μM) in comparison to acarbose (IC50 = 750.0 μM). The limited structure-activity relationships suggested the variation in the inhibitory activities of the compounds affected by different substitutions on the aryl moiety. The enzyme kinetic studies of the most potent compound 9c, revealed that it inhibited α-glucosidase in a competitive mode with a K i value of 4.8 μM. In addition, molecular docking studies investigated the structural perturbation and behavior of all derivatives inside the α-glucosidase active site. Next, molecular dynamic simulations of the most potent compound 9c, were performed to study the behavior of the 9c-complex during the time. The results showed that these compounds can be considered as potential antidiabetic agents.

| S-EPMC10033893 | biostudies-literature

Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors.

Project description:We report herein the design and synthesis of a series of 11 novel tacrine-1,2,3-triazole derivatives via a Cu(i)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. The newly synthesized compounds were evaluated for their inhibition activity against Electrophorus electricus acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) as potential drug targets for Alzheimer's disease (AD). Among the designed compounds, compound 8a2 exhibited potent inhibition against AChE and BChE with IC50 values of 4.89 μM and 3.61 μM, respectively. Further structure-activity relationship (SAR) and molecular modeling studies may provide valuable insights into the design of better tacrine-triazole analogues with potential therapeutic applications for AD.

| S-EPMC6071962 | biostudies-literature

Design, Synthesis, and Biochemical Evaluation of New Triazole Derivatives as Aurora-A Kinase Inhibitors.

Project description:Aurora-A kinase, a key mitosis regulator, is expressed in a cell cycle-dependent manner and has an essential role in maintaining chromosomal stability and the normal progression of the cell through mitosis. Aurora-A kinase is overexpressed in many malignant solid tumors, such as breast, ovarian, colon, and pancreatic cancers. Thus, inhibiting Aurora-A kinase activity is a promising approach for cancer treatment. Here, new triazole derivatives were designed as bioisosteric analogues of the known inhibitor JNJ-7706621. The new compounds showed interesting inhibitory activity against Aurora-A kinase, as attested by IC50s in the low to submicromolar range.

| S-EPMC8469531 | biostudies-literature

Design, synthesis and biological evaluation of benzo-[d]-imidazo-[2,1-b]-thiazole and imidazo-[2,1-b]-thiazole carboxamide triazole derivatives as antimycobacterial agents.

Project description:In the search for new anti-mycobacterial agents, we revealed the importance of imidazo-[2,1-b]-thiazole and benzo-[d]-imidazo-[2,1-b]-thiazole carboxamide derivatives. We designed, in silico ADMET predicted and synthesized four series of novel imidazo-[2,1-b]-thiazole and benzo-[d]-imidazo-[2,1-b]-thiazole carboxamide analogues in combination with piperazine and various 1,2,3 triazoles. All the synthesized derivatives were characterized by 1H NMR, 13C NMR, HPLC and MS spectral analysis and evaluated for in vitro antitubercular activity. The most active benzo-[d]-imidazo-[2,1-b]-thiazole derivative IT10, carrying a 4-nitro phenyl moiety, displayed IC90 of 7.05 μM and IC50 of 2.32 μM against Mycobacterium tuberculosis (Mtb) H37Ra, while no acute cellular toxicity was observed (>128 μM) towards the MRC-5 lung fibroblast cell line. Another benzo-[d]-imidazo-[2,1-b]-thiazole compound, IT06, which possesses a 2,4-dichloro phenyl moiety, also showed significant activity with IC50 2.03 μM and IC90 15.22 μM against the tested strain of Mtb. Furthermore, the selected hits showed no activity towards a panel of non-tuberculous mycobacteria (NTM), thus suggesting a selective inhibition of Mtb by the tested imidazo-[2,1-b]-thiazole derivatives over the selected panel of NTM. Molecular docking and dynamics studies were also carried out for the most active compounds IT06 and IT10 in order to understand the putative binding pattern, as well as stability of the protein-ligand complex, against the selected target Pantothenate synthetase of Mtb.

| S-EPMC9364363 | 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