Computational modeling of selected phytochemicals from Reevesia formosana: mechanistic insights into their potential against lung cancer

Isobonducellin phytocompound from Artemisia annua L. plant exhibits anti-colorectal cancer activity via AKT1 regulation: an in-silico study.

Colorectal cancer (CRC) is one of the leading contributors to cancer related mortality worldwide highlighting the need for novel therapeutic agents. This study investigated the potential anti-colorectal cancer activity of phytochemicals from Artemisia annua L. plant using an integrated in silico approaches. Gene expression analysis, ADMET screening, network pharmacology, molecular docking, density functional theory (DFT), molecular dynamics (MD) simulation, and post-simulation trajectory analyses were employed to identify potential therapeutic compounds and molecular targets. Among the identified phytochemicals, toxicity screening identified 13 predicted non-toxic compounds and molecular docking results revealed that cirsilineol (-8.3 kcal/mol), 3,5-dihydroxy-6,7,3',4'-tetramethoxyflavone (-7.9 kcal/mol), and isobonducellin (-7.9 kcal/mol) exhibited strong binding affinity toward AKT1 protein than control drug 5fu (-5 kcal/mol) and capivasertib (-7.6 kcal/mol). Additionally, ADME analysis confirmed favorable drug likeness profiles of these active compounds. The 200ns molecular dynamics simulation analysis revealed that the isobonducellin-AKT1 complex possessed stable conformation with good RMSD (2.253 ± 0.243 Å), RMSF (1.184 ± 0.852 Å), Rg (4.0 ± 0.064 Å), SASA (45.93 ± 36.75 Å2), and hydrogen bond (84.649 ± 5.306), compared to other ligands and control capivasertib. DFT, PCA, DCCM and MM-GBSA binding free energy analysis further supported isobonducellin (CID: 10423880) as a strong AKT1-targeting drug candidate. Although MM-GBSA suggested slightly better binding for another ligand, isobonducellin was selected based on its overall superior dynamic stability and consistent interaction profile across simulations. Our results proposed that isobonducellin from Artemisia annua L. shows potential as a colorectal cancer therapeutic by modulating multiple signaling pathways and targeting AKT1 protein. However, additional experimental studies such as cancer cell-line assays and animal-model testing are required to validate this study.

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

Computational identification of natural phytochemicals as potential inhibitors of UBE2J1 causing ovarian cancer

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.

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.

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

The exploration of edible mushrooms as sources of bioactive compounds has gained significant attention for their potential role in disease prevention and functional food development. In this study, the phytochemical profile and therapeutic potential of Pleurotus membranaceus (PM) against lung cancer-associated targets were evaluated using integrated in silico and experimental approaches. Gas chromatography-mass spectrometry (GC–MS) analysis identified 23 bioactive constituents, among which ergosterol demonstrated promising therapeutic relevance. Molecular docking analyses revealed that ergosterol exhibited a higher binding affinity (− 9.258 kcal/mol) than the standard anticancer drug Erlotinib (− 8.86 kcal/mol) toward key lung cancer-related targets, including PIM1, HIF1, PI3Kα, and receptor tyrosine kinases (RTKs). Molecular dynamics simulations further supported the structural stability of the ergosterol–PIM1 complex through favourable non-covalent interactions, lower RMSD values, and stable radius of gyration (Rg) profiles relative to the reference drug. These findings suggest that ergosterol derived from Pleurotus membranaceus may represent a promising natural bioactive compound for further investigation as a potential therapeutic candidate against lung cancer.

Mutant-Selective Binding of Phyllanthus niruri Phytochemicals to EGFR T790M: A Quantum-Classical Mechanistic Study

Multiscale quantum-classical in silico predictions of Phyllanthus niruri phytochemicals as non-covalent EGFR T790M binders warranting experimental validation as T790M-directed agents in HCC are presented.