Jul 2026· Indonesian Journal of Chemistry· 0 citations· 24 references
TL;DR
It is suggested that amentoflavone has potential as a natural lead compound for further optimization and development of ERα-targeted therapies in ER-positive breast cancer.
Abstract
Flavones, a subclass of flavonoids, are widely recognized for their diverse biological activities, including antioxidant, anti-inflammatory, and anticancer effects. Amentoflavone, a naturally occurring biflavonoid, has attracted attention for its potential to modulate cancer-related molecular targets. This study investigated the anticancer potential of amentoflavone against estrogen receptor alpha (ERα), a key therapeutic target in ER-positive breast cancer, using an integrated in silico and cytotoxicity approach. Molecular docking analysis using AutoDock4 demonstrated that amentoflavone binds strongly to ERα with a binding affinity of −37.03 kJ/mol and exhibits interaction similarity with the native ligand 4-hydroxytamoxifen (−48.27 kJ/mol). A 100-ns molecular dynamics simulation confirmed the stability of the amentoflavone–ERα complex, as indicated by stable RMSD, RMSF, SASA, and radius of gyration values, along with favorable MM/PBSA binding energy. Cytotoxicity evaluation using the MTT assay in T47D breast cancer cells showed that amentoflavone exhibited moderate cytotoxicity (IC50 = 169.547 ± 34.1651 µg/mL), supported by dose-dependent apoptotic morphological changes. These findings suggest that amentoflavone has potential as a natural lead compound for further optimization and development of ERα-targeted therapies in ER-positive breast cancer.
This research aimed to demonstrate the activity of several promising benzanilide molecules, showing promising growth-inhibitory cytotoxic actions with increasing concentrations against EGFR in breast cancer.
M. Parab, Pramodkumar P. Gupta, S. Shetty et al.· Biotechnology Notes· 0 citations
This study combines ligand- and structure-based in silico strategies to predict the inhibitory activity of natural flavonoids on the Polo-Like Kinase-1 (PLK-1) enzyme as candidate anticancer agents. This enzyme participates in mitosis and is overexpressed in cancer cells. Furthermore, it has been shown to have important implications for tumor metastasis, and its inhibitors are attractive starting points for drug development. First, classification models are developed using linear discriminant analysis and a multilayer perceptron neural network. Models with accuracy greater than 80%, validated using standard statistical performance metrics and applicability domain, are used for virtual screening identifying four compounds as potential antitumor drugs. Subsequently, the identified compounds are evaluated using a molecular docking methodology to verify their binding mode and interactions with the catalytic domain of PLK-1. Finally, the integration of molecular dynamics simulations, at 300 ns, with Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) thermodynamic calculations demonstrates that the hydroxylation pattern of ring B in the flavonol scaffold is the fundamental chemical-structural determinant of electrostatic interactions and the architecture of water-mediated networks. Among the evaluated flavonoids, myricetin showed the most favorable overall computational profile, including the highest virtual-screening score and the most favorable mean MM/GBSA estimate, supporting its prioritization for experimental evaluation as a potential PLK-1 inhibitor. The integration of these approaches offers a robust methodological framework for proposing candidates with a higher probability of success, in subsequent stages of experimental validation, reducing time and costs in the early stages of drug development.
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The findings indicate that GA suppresses lung cancer cell proliferation and migration by inducing oxidative stress and apoptosis through modulation of the AKT–RPS6KB1 signalling pathway, highlighting its potential as a therapeutic candidate for lung cancer.
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Findings highlight Withaferin A as a promising natural inhibitor of UBE2J1 and provide a foundation for future experimental validation aimed at developing targeted therapies against ovarian cancer.
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Among the synthesized compounds, PBc1 exhibited the greatest in vitro antiproliferative activity against both MDA-MB-231 and SK-OV-3 cell lines, suggesting that PBc1 is a promising compound for further biological and mechanistic investigation.
Prachita Gauns Dessai, Parixit J. Bhandurge, C. Nazareth et al.· Journal of the Iranian Chemi...· 0 citations
Breast cancer is a prevalent and aggressive tumor affecting women, known for its molecular diversity and treatment resistance. This study investigates the anticancer potential of Icariin (ICA), a flavonol glycoside derived from Herba epimedii, against breast cancer using network pharmacology and molecular simulation. Using the SwissTargetPrediction database and GeneCards, the researchers identified 98 common targets shared by ICA and breast cancer. Gene ontology (GO) and KEGG enrichment analyses highlighted the targets' roles in the regulation of apoptosis, inflammatory signaling, receptor tyrosine kinase activity, chemokine signaling, sphingolipid metabolism, and VEGF pathways. Molecular docking revealed ICA's strong binding affinity for key oncogenic proteins, with binding energies ranging from −12 to −7.5 kcal/mol, particularly to SER783, THR862, ASP863, LYS753, and ARG849. Molecular dynamics (MD) simulations demonstrated the structural stability of the ICA‐HER2 complex, which maintained strong hydrogen bonds and exhibited minimal conformational changes over a 1000 ns trajectory, with average RMSD values of 1.7 Å for the protein and 1.0 Å for the protein‐ligand complex. Furthermore, ICA exhibited favorable pharmacokinetic properties, including moderate solubility and negligible inhibition of cytochrome P450. These findings support the hypothesis that ICA may serve as a valuable natural compound for treating HER2‐driven breast cancer; it requires further experimental validation.
