What type of study is this?

This is a In Vitro Study study.

August 25, 2025

Evaluation of Annomontine‐Based Anticancer Agents: A Synergistic Computational and Cytotoxicity Approach

Key Points

P3F and P3H exhibit stronger anticancer activity than existing EGFR inhibitors, highlighting their potential as second-generation agents.
Binding affinity assessments show P3F and P3H outperform FDA-approved drugs like osimertinib and toceranib in computational docking studies.
A combination of computational modeling and in vitro testing confirms the efficacy and safety of the designed annomontine derivatives in targeting EGFR.
The study identifies several potent compounds with favorable pharmacokinetic profiles, indicating their promise in cancer treatment.

Abstract

Abstract EGFR is an important target for cancer treatment owing to its role in tumor growth and resistance. Annomontine alkaloids show anticancer potential, but their EGFR inhibition remains underexplored. This study aimed to test a set of annomontine‐derived compounds as anticancer agents against EGFR utilizing a mixture of computational and in‐vitro methods. Twenty three annomontine derivatives were designed and optimized using DFT. In‐silico methodologies like docking, simulation, and ADMET were employed to assess their binding affinity to EGFR with pharmacokinetic properties, prediction and cytotoxicity was confirmed via in vitro. Docking studies revealed P3F (−9.45 kcal/mol), P3H (−9.65 kcal/mol), and P3G (−9.39 kcal/mol) as the best hit compounds, superior to the activity of FDA‐approved EGFR inhibitors such as osimertinib (−6.32 kcal/mol), toceranib (−7.98 kcal/mol). MD confirmed the integrity of the protein–ligand contacts, while ADMET profiling showed good solubility, permeability, and low toxicity. Cytotoxicity assays revealed that P3F (IC 5 ₀ = 0.26 µM) and P3H (IC 5 ₀ = 0.37 µM) exhibit greater potency than reference drugs. These findings suggest that P3F and P3H are promising candidates for the development of second‐generation EGFR inhibitors, combining strong binding, favorable pharmacokinetics, and superior anticancer activity.

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