In silico evaluation of Syzygium cumini phytochemicals as BCL-2 inhibitors: molecular docking and molecular dynamics simulations for gastric cancer therapy

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.

Exploration of Compounds Identified from Amomum cardamomum Seed Extract: LC-MS Profiling, Network Pharmacology, and Computational Analyses for Innovative Multi-Targeted Breast Cancer Therapy

Background Breast cancer remains one of the leading causes of cancer-related mortality worldwide, and the emergence of drug resistance, systemic toxicity, and limited efficacy of current therapies highlight the need for safer and more effective treatment. Natural products have emerged as promising sources of multi-target anticancer agents. A. cardamomum has demonstrated preliminary anticancer potential, yet the bioactive constituents and their molecular mechanisms in breast cancer remain poorly elucidated. Methods This study integrated in silico approaches to investigate the therapeutic potential of A. cardamomum seed extract against breast cancer. LC–MS analysis identified phytochemical compounds, followed by network pharmacology to determine their potential targets and molecular pathways. Pharmacokinetic and toxicity predictions were assessed through ADMET and Lipinski’s rule of five analyses to evaluate drug-likeness and safety. Molecular docking and molecular dynamics (MD) simulations were conducted to evaluate binding affinity and structural stability of compounds with key oncogenic proteins. Results LC-MS profiling identified 22 distinct compounds in A. cardamomum seeds. ADMET and Lipinski analyses demonstrated that most compounds possessed high gastrointestinal absorption, favorable oral bioavailability, and low toxicity risk. Network pharmacology highlighting SRC, TNF-α, Caspase-3, and EGFR as central nodes in the protein-protein interaction network. Molecular docking identified compounds C17 and C20 as the most promising bioactives, showing strong binding affinities and interactions similar to control ligands. MD simulations confirmed their stable complexes, indicating conformational stability and robust ligand–protein interactions. Conclusion This study highlights the promising multi-target anticancer potential of A. cardamomum seeds. Compounds C17 and C20 were identified as lead candidates with strong and stable interactions with key breast cancer-related proteins and favorable pharmacokinetic properties. These results suggest that A. cardamomum could serve as a potential source for developing new plant-based therapies against breast cancer. Further in vitro and in vivo investigations are warranted to validate their efficacy and safety.

Integrated in silico and experimental evaluation of ergosterol from Pleurotus membranaceus against lung cancer

The phytochemical profile and therapeutic potential of Pleurotus membranaceus against lung cancer-associated targets were evaluated and ergosterol derived from Pleurotus membranaceus may represent a promising natural bioactive compound for further investigation as a potential therapeutic candidate against lung cancer.

Active ingredients and molecular targets of Tripterygium wilfordii against colorectal cancer: network pharmacology, molecular docking, molecular dynamics simulations and in vitro evaluation

Colorectal cancer (CRC) is one of the common malignant tumors of the gastrointestinal tract, encompassing both colon cancer and rectal cancer. This study explores the therapeutic potential of T. wilfordii in CRC through network pharmacology, molecular docking, and in vitro experiments. Active components of T. wilfordii were screened using oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18) criteria. Protein–protein interaction network analysis, gene ontology functional enrichment, and kyoto encyclopedia of genes and genomes pathway enrichment were performed to identify candidate targets and signaling pathways. Molecular docking and molecular dynamics simulations were used to predict compound–target binding modes and to assess the dynamic stability of selected docked complexes. In vitro experiments, including CCK-8 assay, EGFR kinase activity assay, EGF rescue assay, and Western blot analysis, were conducted to evaluate the anticancer activity of key components and the involvement of EGFR signaling in CRC cell lines (HT29 and HCT116). A total of 51 active compounds were identified from T. wilfordii, with 23 core components selected for further analysis. PPI network analysis identified TP53, AKT1, EGFR, STAT3, and mTOR as central candidate targets, and KEGG enrichment analysis highlighted cancer-related pathways including PI3K/Akt, Wnt/β-catenin, and mTOR. Molecular docking, interpreted with target-specific reference-ligand redocking benchmarks, prioritized several core components, including β-Sitosterol (Lei3), Tryptophenolide (Lei4), Tripterifordin (Lei8), Isoxanthohumol (Lei9), and Stigmasterol (Lei16), as compounds with favorable AutoDock Vina docking scores toward EGFR. MD simulations supported the relative stability of the docked EGFR-Lei4 complex under the simulation conditions. In vitro EGFR kinase activity assay showed that Lei4 directly inhibited recombinant EGFR kinase activity in a concentration-dependent manner, with an IC50 value of 1.38 ± 0.12 μM. In cell-based assays, Lei4 inhibited HT29 and HCT116 cell proliferation in a dose-dependent manner, with IC50 values of 27.98 ± 3.56 μM and 28.0 ± 3.6 μM, respectively. EGF partially reversed Lei4-induced proliferation inhibition, and Western blot analysis showed that Lei4 decreased the phosphorylation levels of EGFR, ERK1/2, and JUN without markedly altering total protein expression. T. wilfordii may exert anti-CRC effects through a multi-component, multi–target, and multi-pathway mechanism. Tryptophenolide (Lei4) showed moderate but reproducible anti-CRC activity and directly inhibited EGFR kinase activity in vitro, supporting EGFR pathway inhibition as one mechanism contributing to its cellular effects. These findings provide a basis for further optimization and mechanistic evaluation of T. wilfordii -derived active compounds in CRC.

Computational Evaluation of the Anticancer Potential of Celastrus paniculatus: An Integrative Approach using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

In Silico Investigation of Syzygium cumini Phytoconstituents Against Pancreatic Cancer Using Network Pharmacology and Molecular Docking

Background - The present study focuses on the investigation of the therapeutic potential of Syzygium cumini phytoconstituents against pancreatic cancer using integrated network pharmacology and molecular docking approaches. Syzygium cumini, commonly known as jamun, is a medicinal plant widely recognized for its rich phytochemical composition and diverse pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, and anticancer properties. Several bioactive compounds present in the plant have shown promising effects against various cancer-related pathways and molecular targets. Methods - Bioactive phytoconstituents of Syzygium cumini were identified using phytochemical and bioinformatics databases including imppat and pubchem. Drug-likeness, pharmacokinetic, and toxicity properties were evaluated through ADMET analysis. Potential pancreatic cancer-associated targets were retrieved using Genecards, UniProt, Swiss target prediction databases. Network pharmacology analysis was performed to identify compound-target interactions, protein-protein interaction networks, hub genes, and significant signaling pathways using string and Cytoscape software. Furthermore, molecular docking studies were carried out to evaluate the binding affinity and protein-ligand interaction profiles of selected phytoconstituents with major pancreatic cancer target proteins. Results - The integrated computational analysis revealed significant interactions between selected phytoconstituents and pancreatic cancer-associated target proteins. Several compounds demonstrated favorable drug-likeness properties, strong binding affinity, and stable molecular interactions with key proteins involved in cancer progression, apoptosis, inflammation, and cell proliferation. Network pharmacology findings indicated the involvement of multiple signaling pathways associated with pancreatic carcinogenesis. Conclusions - Based on the obtained results, syzygium cumini phytoconstituents exhibited promising anticancer potential against pancreatic cancer through multi-target mechanisms. The study provides a scientific basis for the development of novel plant-derived therapeutic agents and highlights the importance of network pharmacology and molecular docking approaches in modern drug discovery research against pancreatic cancer.