Evidence map›Paper›PMID 39009798›Full record

ArticleMolecular neurobiology2025

Synthesis and Neurobehavioral Evaluation of a Potent Multitargeted Inhibitor for the Treatment of Alzheimer's Disease.

Mohd Shahnawaz Khan, Zuber Khan, Nasimudeen R Jabir, Sidharth Mehan, Mohd Suhail, Syed Kashif Zaidi, Torki A Zughaibi, Mohammad Abid, Shams Tabrez

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
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

9 authors.

Mohd Shahnawaz Khan *Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Zuber Khan *Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga, 142001, Punjab, India.
Nasimudeen R JabirDepartment of Biochemistry, Centre for Research and Development, PRIST University, Vallam, Thanjavur, Tamil Nadu, India.
Sidharth MehanDepartment of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga, 142001, Punjab, India. sidh.mehan@gmail.com.
Mohd SuhailKing Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Syed Kashif ZaidiCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
Torki A ZughaibiKing Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Mohammad AbidMedicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India. mabid@jmi.ac.in.
Shams TabrezKing Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. shamstabrez1@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) poses a significant health challenge worldwide, affecting millions of individuals, and projected to increase further as the global population ages. Current pharmacological interventions primarily target acetylcholine deficiency and amyloid plaque formation, but offer limited efficacy and are often associated with adverse effects. Given the multifactorial nature of AD, there is a critical need for novel therapeutic approaches that simultaneously target multiple pathological pathways. Targeting key enzymes involved in AD pathophysiology, such as acetylcholinesterase, butyrylcholinesterase, beta-site APP cleaving enzyme 1 (BACE1), and gamma-secretase, is a potential strategy to mitigate disease progression. To this end, our research group has conducted comprehensive in silico screening to identify some lead compounds, including IQ6 (SSZ), capable of simultaneously inhibiting the enzymes mentioned above. Building upon this foundation, we synthesized SSZ, a novel multitargeted ligand/inhibitor to address various pathological mechanisms underlying AD. Chemically, SSZ exhibits pharmacological properties conducive to AD treatment, featuring pyrrolopyridine and N-cyclohexyl groups. Preclinical experimental evaluation of SSZ in AD rat model showed promising results, with notable improvements in behavioral and cognitive parameters. Specifically, SSZ treatment enhanced locomotor activity, ameliorated gait abnormalities, and improved cognitive function compared to untreated AD rats. Furthermore, brain morphological analysis demonstrated the neuroprotective effects of SSZ, attenuating Aβ-induced neuronal damage and preserving brain morphology. Combined treatment of SSZ and conventional drugs (DON and MEM) showed synergistic effects, suggesting a potential therapeutic strategy for AD management. Overall, our study highlights the efficacy of multitargeted ligands like SSZ in combating AD by addressing the complex etiology of the disease. Further research is needed to elucidate the full therapeutic potential of SSZ and the exploration of similar compounds in clinical settings, offering hope for an effective AD treatment in the future.

Indexed as

Alzheimer DiseaseBehavior, AnimalAmyloid beta-PeptidesAnimalsDisease Models, AnimalHumansMaleRatsRats, Sprague-DawleyAmyloid beta-PeptidesAlzheimer’s diseaseBeta-amyloidNeurodegenerationNeuroprotectionSSZ

Identifiers

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.