Jul 2026· Indonesian Journal of Chemistry· 0 citations· 34 references
TL;DR
Mangostanol and 9-hydroxycalabaxanthone will be prioritized for in vitro/in vivo testing, underscoring the importance of a stepwise, structure-based approach to identify plant-based natural compounds targeting XIAP-BIR3.
Abstract
Hepatocellular carcinoma (HCC) exhibits apoptosis resistance driven in part by overexpression of X-associated inhibitor of apoptosis protein (XIAP), whose baculovirus IAP repeat domain 3 (BIR3) suppresses caspase activation. This study employed a stepwise in silico workflow to identify plant-based natural compounds targeting XIAP-BIR3. A curated library of 534 compounds from 12 medicinal plants was screened using ensemble docking (AutoDock Vina), then filtered for drug-likeness, and their poses were generated with AutoDock4. Selected candidates were evaluated through conventional molecular dynamics (MD) simulations (50 and 500 ns) and Parallel Cascade Selection MD (PaCS-MD). As a result, mangostanol and 9-hydroxycalabaxanthone showed the best affinity and stability, comparable to the co-crystal ligand 7HU as a control, while neoandrographolide showed decreased stability in the 500 ns MD simulation. PaCS-MD confirmed that 9-hydroxycalabaxanthone has a stronger initial interaction energy than neoandrographolide, but eventually fully dissociates, consistent with a dynamic and reversible interaction. Overall, mangostanol and 9-hydroxycalabaxanthone will be prioritized for in vitro/in vivo testing, underscoring the importance of a stepwise, structure-based approach.
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.
N. M. Arulmozhi, Thiyagarajan G· Applied Biochemistry and Bio...· 0 citations
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.
Zujaja Rehman, Ejaz Rasul, Wisha Asif et al.· In Silico Pharmacology· 0 citations
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.
Su Bo, Yongsheng Liao, Xiaofeng Chen et al.· 3 Biotech· 0 citations
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.
Md. Naziur Rahman, Abu Yousuf Hossin, S. Talukder et al.· PLoS ONE· 0 citations
Computational predictions of potential interactions between selected cinnamon-derived phytochemicals and cancer-associated signaling proteins are provided and are consistent with the preliminary observation that the crude cinnamon extract exhibits antioxidant activity and cytotoxic effects in colorectal cancer cell lines.
R. Raut, S. Anwar, Reem A. Alromaihi et al.· Current Issues in Molecular...· 0 citations
The identification of marine-derived compounds addresses the need to overcome resistance to single-checkpoint immunotherapy and are regarded as earlystage lead scaffolds requiring structural optimization rather than hits with acceptable overall safety profiles.
Jeevan Patra, Surya Nath Pandey, Harishchandra Verma et al.· Current Chemical Biology· 0 citations
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