Evidence map›Paper›PMID 40798865›Full record

ArticleCancer reports (Hoboken, N.J.)2025

Flavonoids as Promising Akt1 Inhibitors in Cancer Medicine: Insights From Molecular Docking, Dynamics, DFT Calculations, and In Vitro Validation.

Shokoofeh Jamshidi, Ali Eghbalian, Setareh Shojaei, Amir Taherkhani, Mehran Feizi-Dehnayebi

Abstract read
In one paragraph

Article in Cancer reports (Hoboken, N.J.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Pharmacogenomic andFrontiers in pharmacology · 2025
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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

5 authors.

Shokoofeh JamshidiDepartment of Oral and Maxillofacial Pathology, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran.ORCID 0000-0002-0646-1882
Ali EghbalianDepartment of Oral and Maxillofacial Pathology, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran.ORCID 0009-0001-3862-026X
Setareh ShojaeiDepartment of Oral and Maxillofacial Pathology, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran.ORCID 0000-0001-8323-1231
Amir TaherkhaniResearch Center for Molecular Medicine, Institute of Cancer, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran.ORCID 0000-0002-6546-8785
Mehran Feizi-DehnayebiDepartment of Organic Chemistry, Faculty of Chemistry, Alzahra University, Tehran, Iran.ORCID 0000-0002-7868-9085

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe PI3K/Akt/mTOR signaling pathway is commonly deregulated in different types of cancers, contributing to tumor proliferation, persistence, and resistance to treatment. Akt1, a crucial kinase within this pathway, plays a critical role in tumor progression and the occurrence of therapeutic resistance. The emergence of resistance is a significant challenge in cancer therapy. Targeted therapies offer a promising method to overcome this challenge. Akt1 presents a promising target for therapeutic intervention.

aimsThis study aimed to evaluate the binding affinities of 61 flavonoid-derived natural compounds to the Akt1 ATP-binding site using molecular docking with AutoDock to identify potential Akt1 inhibitors.

methodsCross-validation and Density Functional Theory analysis were conducted utilizing the SwissDock server and the Gaussian 09 W software suite for the top-ranked compounds. Following energy minimization, semi-flexible docking of flavonoids and the control inhibitor Ipatasertib was performed against the Akt1 ATP-binding pocket. Binding modes were analyzed using Discovery Studio Visualizer. Molecular dynamics simulations were conducted to assess the conformational stability and binding durability of the highest-scoring Akt1 inhibitor complex identified through molecular docking analyses. The pharmacokinetics and toxicity properties of the most potent Akt1 inhibitors were evaluated using the PreADMET tool. Also, the effect of the most potent Akt1 inhibitor on cell viability was studied in vitro through the 2,5-diphenyl-2H-tetrazolium bromide approach. Besides, the most promising compound was evaluated for its impact against the FOXO3 (an Akt1 downstream target) gene expression in MCF-7 cells.

resultsKaempferol 3-rutinoside-4'-glucoside and Kaempferol 3-rutinoside-7-sophoroside displayed exceptional binding affinities (ΔG

conclusionsComputational analyses identified flavonoids, particularly Kaempferol glycosides, as potential Akt1 inhibitors with significantly higher predicted binding affinities than Ipatasertib. These findings warrant further exploration of the therapeutic potential of flavonoids for cancers driven by Akt1 hyperactivation.

Indexed as

FlavonoidsNeoplasmsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktCell ProliferationDensity Functional TheoryHumansMCF-7 CellsMolecular Docking SimulationMolecular Dynamics SimulationPiperazinesPyrimidinesAKT1 protein, humanFlavonoidsipatasertibPiperazinesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPyrimidinesAkt1cancerdrugflavonoidmolecular docking

Identifiers

PMID40798865
PMCPMC12343748

What Socratic holds

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Registered trials

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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.