Evidence map›Paper›PMID 40325541›Full record

ArticleMedicinal chemistry (Shariqah (United Arab Emirates))2026

Design, Synthesis, and Biological Evaluation of a Novel Series of Thiazolidinediones as Dual GSK-3β and Tau Aggregation Inhibitors.

Zahra Abdollahi, Khalil Abnous, Mohamad Reza Kalani, Seyed Mohammad Taghdisi, Somaieh Soltani, Mojgan Nejabat, Farzin Hadizadeh

Abstract read
PubMed Publisher
In one paragraph

Article in Medicinal chemistry (Shariqah (United Arab Emirates)), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Zahra AbdollahiDepartment of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Khalil AbnousPharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Mohamad Reza KalaniSchool of Cell and Molecular Biology, University of Illinois at Urbana-Champaign, Urbana, United States.
Seyed Mohammad TaghdisiTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Somaieh SoltaniDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, 51664- 14766, Iran.
Mojgan NejabatDepartment of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.ORCID 0000-0001-8638-4989
Farzin HadizadehDepartment of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Funding

Iran National Institute of Science Foundation (INSF) 99022631Research Deputy of Mashhad University of Medical Sciences 981617
6 · The paper itself

Abstract

introductionGlycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase that is involved in the synthesis of glycogen. Among the inhibitors, thiazolidinediones (TZDs) can specifically bind to GSK-3β. They act non-competitively with ATP, and as a result, they are very specific and have fewer side effects. In this research, new TZDs were designed and synthesized, and then their inhibitory effects on GSK-3β enzyme and tau aggregation were investigated. MATERIALS AND

methodsThe structure of the compounds was confirmed using 1H-NMR, 13CNMR, and LC-MASS. The inhibitory activities of the compounds 5a-p, against GSK-3β were evaluated using Z'-LYTE technique, and the IC50 values were determined.

resultsCompound 5l (R1 = Me, R2 = 4-F-benzyl, R3 = butyl) with IC50 of 16.1 μM exhibited the most potent inhibition. Also, the binding with tau protein and their inhibitory effects on the accumulation of recombinant human tau protein (1N4R, htau34) were evaluated using the Surface Plasmon Response (SPR) method. In this study also the impact of TZDs on tau aggregation using the Thioflavin T (ThT) assay was investigated. PC12 cells viability study confirmed the neuroprotective effects of compounds against tau aggregates. MD simulation studies showed the interaction of 5l with the active site of GSK-3β (PDB ID: 2OW3) and also its destructive effect on tau aggregate (PDB ID: 5O3L) was studied.

conclusionOverall, the study identified three promising TZDs with potential as inhibitors of GSK-3β and tau proteins, highlighting compound 5l as particularly effective in stabilizing GSK- 3β and disrupting tau aggregation.

Indexed as

Drug DesignGlycogen Synthase Kinase 3 betaProtein Kinase Inhibitorstau ProteinsThiazolidinedionesAnimalsDose-Response Relationship, DrugHumansMolecular Docking SimulationMolecular StructurePC12 CellsProtein AggregatesRatsStructure-Activity RelationshipGlycogen Synthase Kinase 3 betaProtein AggregatesProtein Kinase Inhibitorstau ProteinsThiazolidinedionesGlycogen synthase kinase-3βsynthesistau-aggregationtau proteinsthiazolidinedioneZ'-LYTE technique

Identifiers

PMID40325541

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.