Molecular and metabolic dysregulation of lung cancer in developing anti-tumor activity by gambogic acid mediated mTOR signaling: in vitro and computational study

In silico and in vitro evaluation of synergistic anticancer effects of erucin and kaempferol from Eruca sativa against human A549 non-small cell lung cancer cells (NSCLC)

Computational Investigation of Cinnamon Phytochemicals Targeting Key Cancer Signaling Pathways: Molecular Docking, ADMET and Molecular Dynamics Simulations Analysis

Cancer remains one of the leading causes of morbidity and mortality worldwide, highlighting the need for safe and effective therapeutic strategies targeting multiple oncogenic pathways. Cinnamon (Cinnamomum spp.) contains several bioactive phytochemicals with reported antioxidant and anticancer properties; however, their potential interactions with key cancer-associated signaling proteins have not been comprehensively investigated. In this study, an integrated computational and preliminary experimental approach was employed to evaluate four major cinnamon phytochemicals, namely e-cinnamaldehyde, eugenol, p-cymene, and cinnamic acid. Consensus molecular docking was performed using AutoDock Vina (v1.2.7), Smina (v2020.12.10), and GNINA (v1.3.3) against phosphoinositide 3-kinase (PI3K), nuclear factor kappa B (NF-κB), and mammalian target of rapamycin (mTOR). Docking analyses were complemented by protein-ligand interaction profiling, pharmacokinetic and toxicity prediction (ADMET), and a 100 ns molecular dynamics simulation with MM/GBSA binding free-energy analysis of the selected mTOR-p-cymene complex. In addition, the antioxidant activity and cytotoxic effects of a crude methanolic cinnamon bark extract were evaluated using in vitro antioxidant assays and MTT assays against HCT-116 and HT-29 colorectal cancer cell lines. Consensus docking predicted that all four phytochemicals were capable of interacting with the selected protein targets, although the predicted binding profiles varied among the compounds. Eugenol showed comparatively more favorable predicted interactions with PI3K, p-cymene produced the lowest predicted docking score for NF-κB, and cinnamic acid displayed a comparatively consistent predicted multitarget binding profile across PI3K, NF-κB, and mTOR. ADMET analysis suggested that all compounds satisfied major drug-likeness criteria and exhibited predicted oral bioavailability, although potential cytochrome P450 interactions and hepatotoxicity were predicted for some compounds. Molecular dynamics simulation indicated that the selected mTOR-p-cymene complex maintained a stable binding pose throughout the simulation, while MM/GBSA analysis yielded a modest binding free-energy estimate (ΔG_bind = −4.70 ± 8.20 kcal/mol), which should be interpreted cautiously because of the observed energetic variability. The crude methanolic cinnamon bark extract exhibited antioxidant activity and reduced the viability of HCT-116 and HT-29 colorectal cancer cells in a concentration-dependent manner. Collectively, these findings provide computational predictions of potential interactions between selected cinnamon-derived phytochemicals and cancer-associated signaling proteins and are consistent with the preliminary observation that the crude cinnamon extract exhibits antioxidant activity and cytotoxic effects in colorectal cancer cell lines. However, the computational analyses do not establish direct inhibition of the PI3K/NF-κB/mTOR signaling pathway, and the biological assays were performed using a crude extract rather than isolated phytochemicals. Therefore, further studies using purified compounds, biochemical target validation, pathway-specific cellular analyses, and in vivo models are required to determine whether the predicted protein-ligand interactions contribute to the observed biological activity.

Exploring the Breast Cancer Inhibitor from Flavone Subclass: In Silico and In Vitro Assays

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.

Computational identification and evaluation of Adenium obesum phytochemicals as potential EGFR inhibitors for targeted therapy against non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) remains the leading cause of lung cancer–related mortality, largely driven by aberrant activation of the epidermal growth factor receptor (EGFR). Despite the clinical success of EGFR tyrosine kinase inhibitors (TKIs), intrinsic and acquired resistance, coupled with safety concerns, highlight the need for novel, safer inhibitors. Natural products represent an underexplored source of structurally diverse bioactive compounds with favorable biocompatibility. In this study, a comprehensive in silico approach is used to evaluate phytochemicals from Adenium obesum as potential candidate EGFR-targeting compound. Initially, sixteen phytochemicals were first assessed for predicted antineoplastic activity using PASS. High-scoring molecules were docked against the EGFR kinase domain (PDB ID: 1M17), besides performed detailed protein–ligand interaction analysis, drug-likeness and ADMET profiling, toxicity prediction and 100-ns molecular dynamics (MD) simulations. PASS-based bioactivity prediction revealed strong anticancer potential among the sixteen screened compounds, with consistently high antineoplastic and antiproliferative activity probabilities (Pa > 0.79) and low inactivity scores, supporting their selection for subsequent docking, ADMET, and molecular dynamics analyses. Next, several phytochemicals exhibited strong docking affinities, with Cardenolide achieving the highest binding score (–9.9 kcal/mol) and forming stable interactions with key catalytic residues. A 100-ns MD simulation confirmed the structural stability, persistent binding, and dynamic integrity of the EGFR–Cardenolide complex under physiological conditions. Importantly, interaction mapping revealed that Cardenolide engages conserved and functionally critical regions of the EGFR kinase domain associated with catalytic activity and structural stability, supporting its mechanistic relevance as an ATP-competitive scaffold. Additionally, predicted pharmacokinetic and toxicity profiles further supported Cardenolide’s suitability as a drug-like candidate. Collectively, these results identify Cardenolide as a computationally prioritized candidate with favorable predicted EGFR-binding characteristics, structural stability, and physicochemical and toxicity profiles. However, as the present study is based entirely on computational analyses, these findings should be considered hypothesis-generating and do not establish EGFR inhibitory activity or therapeutic efficacy. Experimental validation, including biochemical kinase inhibition and cellular assays, is therefore required to determine the actual EGFR inhibitory potential and anticancer activity of Cardenolide. Nevertheless, the findings provide a rational basis for prioritizing Cardenolide for further experimental investigation and illustrate the potential of Adenium obesum phytochemicals as a source of candidate EGFR-targeting compounds for future NSCLC drug discovery.

Structure-Based Design and Evaluation of Coumarin-Derived CDK4 Inhibitors for Non-Small Cell Lung Cancer: An Integrated Computational Study.

Findings establish coumarin-derived scaffolds as promising starting points for the development of next-generation CDK4-targeted therapeutics and provide a strong computational foundation for future experimental validation in NSCLC.

Molecular Docking and Pharmacological In Silico Evaluation of Genistein and Hematoxylin as Promising Ribonucleotide Reductase-targeted Therapies for Cancer.

Genistein and hematoxylin demonstrate promising molecular interactions and pharmacological profiles as potential natural RR inhibitors and supports further preclinical development as anticancer agents.