Evidence map›Paper›PMID 41317387›Full record

ArticleChemistry & biodiversity2026

Indenoquinoxaline-Based Spiro-Heterocycles: Synthesis, Structural Characterization, MEDT Study, and Dual Inhibition of Kinase-Related Enzymes EGFR and VEGFR2.

Abdulmajeed Abdullah Alayyaf, Abdullah Saleh Alamary, Mohammad Shahidul Islam, M Ali, Assem Barakat, Ahmed Bari, Luis R Domingo, Khaled M Darwish, Mona A Khamis, Marwan Emara and 3 more

Abstract read
In one paragraph

Article in Chemistry & biodiversity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

13 authors.

Abdulmajeed Abdullah AlayyafDepartment of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.ORCID https://orcid.org/0009-0000-3377-4115
Abdullah Saleh AlamaryDepartment of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Mohammad Shahidul IslamDepartment of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
M AliDepartment of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Assem BarakatDepartment of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.ORCID https://orcid.org/0000-0002-7885-3201
Ahmed BariDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Luis R DomingoIndependent Researcher, Valencia, Spain.
Khaled M DarwishMedicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Mona A KhamisCenter for Aging and Associated Diseases, Zewail City of Science, Technology and Innovation, Giza, Egypt.
Marwan EmaraCenter for Aging and Associated Diseases, Zewail City of Science, Technology and Innovation, Giza, Egypt.
Amany M ElshamyMedical Laboratory Science Department, School of Allied Health Sciences, Badr University in Cairo (BUC), Badr City, Cairo, Egypt.
Tebyan O MirganyDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Mohamed S NafieDepartment of Chemistry, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates.ORCID https://orcid.org/0000-0003-4454-6390

Funding

Ongoing Research Funding program ORF-2025-527
6 · The paper itself

Abstract

A new series of spiro-heterocycles derived from pyrazole-indenoquinoxaline scaffolds 4a-n and 5a-m was designed and synthesized via one-pot multi-component reaction-based a [3 + 2] cycloaddition reaction (32CA). The Molecular Electron Density Theory (MEDT) has been used to theoretically study the 32CA reaction between azomethine ylide (AY) 6a and the electrophilic ethylene 1a. This 32CA reaction, which proceeds via a two-stage one-step mechanism, yields the spiro-cycloadduct 4a with high ortho/endo selectivity. The newly pyrazole-tethered indenoquinoxaline-based spiro-heterocycles 4a-n and 5a-m were evaluated for their anticancer activities against MCF-7 and HepG-2 cancer cell lines. These compounds were targeted as dual EGFR/VEGFR-2 kinase inhibitors. Interestingly, 4l exhibited the most substantial inhibitory effect, with a potent effect on HepG2 cells (1.35 µM) and poor cytotoxicity on MCF-7 (≥50 µM). However, compound 4f displayed a unique antiproliferative potency on HepG2 cells (7.9 µM) and a promising cytotoxicity in MCF-7 (13.5 µM), compared to sorafenib with IC

Indexed as

Antineoplastic AgentsHeterocyclic CompoundsProtein Kinase InhibitorsQuinoxalinesSpiro CompoundsVascular Endothelial Growth Factor Receptor-2ApoptosisCell ProliferationDensity Functional TheoryDose-Response Relationship, DrugDrug Screening Assays, AntitumorErbB ReceptorsHumansMolecular StructureStructure-Activity RelationshipAntineoplastic AgentsEGFR protein, humanErbB ReceptorsHeterocyclic CompoundsKDR protein, humanProtein Kinase InhibitorsQuinoxalinesSpiro CompoundsVascular Endothelial Growth Factor Receptor-23 + 2] cycloaddition (32CA)EGFR/VEGFR‐2 inhibitionindenoquinoxalineMolecular Electron Density Theory (MEDT)spirooxindoles

Identifiers

PMID41317387
PMCPMC13421948

What Socratic holds

Textmetadata
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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.