Jul 2026· Computers in Biology and Medicine· Vol 213, pp.
111854
· 0 citations· 103 references
Medicine
TL;DR
The results proposed that isobonducellin from Artemisia annua L. plant shows potential as a colorectal cancer therapeutic by modulating multiple signaling pathways and targeting AKT1 protein as a strong AKT1-targeting drug candidate.
Abstract
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.
P predictive findings suggest that specific M. champaca flower constituents possess strong targeted binding potential against PTEN and CXCR4 nodes, establishing a validated computational foundation that warrants downstream in vitro and in vivo functional experimental validation.
Saketh Tenkashala Guruprasad, Karthik Punniyakoddi, V. Karthick et al.· Journal of Computational Bio...· 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
Breast cancer is the most frequently diagnosed malignancy in women globally, representing a major global health burden, with a significant subset of cases exhibiting resistance to standard therapeutic regimens. Recently, m6A RNA demethylases such as FTO have been identified as important oncogenes in breast cancer, which modify the epitranscriptome of tumor cells to favor expression of growth-promoting genes while suppressing expression of anti-apoptotic genes. In this study, we performed virtual screening of 1,000 dietary compounds targeting the FTO protein in order to discover potential therapies for breast cancer. 7-Deshydroxypyrogallin-4-carboxylic acid (DCA) was identified as the top-ranked candidate. Molecular dynamics (MD) simulations of DCA-FTO complex displayed the formation of stable hydrogen bonds for 200 ns of MD simulations. The ADMET-prediction of DCA showed high gastrointestinal tract absorption and is not expected to be Ames-toxic. The effect of DCA on the growth of MCF-7 human breast cancer cells was assessed by Sulforhodamine B (SRB) cytotoxicity assays and found to be dose- and time-dependent. The IC₅₀ values for the growth inhibition of MCF-7 breast cancer cells were found to be 90.7 µg/mL (365.4 µM) after 24 h of treatment and 40.8 µg/mL (164.4 µM) after 48 h. As a secondary exploratory analysis, lupinine was computationally evaluated against NQO1; however, its suboptimal binding stability and safety concerns preclude experimental advancement at this stage. These findings provide a preliminary mechanistic and experimental framework for DCA as a dietary FTO inhibitor in breast cancer, necessitating further validation through orthogonal target engagement assays, m6A quantification, and in vivo tumor models.
Shuaib Pasha, S. Harishkumar, Revanth Handralu Chandraiah et al.· Naunyn-Schmiedeberg's Archiv...· 0 citations
Abstract Given that ovarian cancer is a major health concern for women worldwide, we explored the potential of Indian medicinal plants, namely Curcuma longa (Turmeric), Azadirachta indica (Neem), and Asparagus racemosus (Shatavari) via a combined approach of network pharmacology and molecular docking. Initially, bioactive phytochemicals of these plants were sourced from the IMPPAT and SwissTargetPrediction databases, resulting in the identification of 202 compounds along with 1,124 corresponding protein targets. These were then compared with ovarian cancer–related genes obtained from the GeneCards database, leading to the identification of 885 common targets. A protein–protein interaction network was constructed and analyzed using Cytoscape to identify the cluster modules. Additionally, gene ontology and pathway enrichment analyses revealed the multifaceted nature of ovarian cancer, indicating its disruptive impact on various cellular processes, signaling pathways, immune responses, and metabolic regulations. Importantly, EGFR, PIK3CA, JAK2, and PIK3CD were identified as crucial therapeutic nodes within the network. Subsequent molecular docking recognized the strong binding affinity between the active compounds and these key targets, thereby supporting the network analysis. In conclusion, the study highlighted the therapeutic action of C. longa, A. indica, and A. racemosus in combating ovarian cancer and promoting the development of plant-based treatments for this cancer.
Seneha Santoshi, Aastha Tanwar, Riddhi Bahri et al.· Zeitschrift für Naturforschu...· 0 citations
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.
Dessy Arisanty, S. Khairani, K. Cuandra et al.· F1000Research· 0 citations
Introduction: Globally, the incidence of cancer is rising at an alarming rate. Among various types, breast cancer was reported as the most prevalent cancer in females in 2022, while melanoma represents an aggressive form of skin cancer characterized by the malignant transformation of melanocytes. To address the urgent need for new anticancer drugs, traditional medicinal plants offer significant potential. Tetracera macrophylla is widely used by the inhabitants across Asia and Africa to treat diverse ailments, making it a promising candidate for investigation. The objective of the current study was to prepare a polar compound-based methanol extract of T. macrophylla leaves and identify bioactive compounds with potential anticancer activity. Methods: A sequential extraction technique was employed to obtain the methanol extract enriched in polar compounds, which was subsequently analysed using Q-ToF LCMS for compound identification. The identified compounds were then screened in silico against two cancer-related proteins (PDB IDs: 3OG7 and 3ERT) to evaluate their potential against melanoma and breast cancer. Lead compound selection was further refined through physicochemical and pharmacokinetic parameter assessments. Results: The methanol extract (yield: 9.29%) revealed ten compounds, predominantly flavonoids. Molecular docking analysis demonstrated favourable binding energies and interactions of these compounds with the target proteins. Notably, eight compounds namely isovitexin, epigallocatechin 3-O-caffeate, 5,7,4'-trihydroxyflavanone 7-sulfate, 7,8,4'-trihydroxyflavanone, 4,2',3',4'-tetrahydroxychalcone, urolithin A-3-O-glucuronide, epifisetinidol-4alpha-ol, and epicatechin monogallate exhibited drug-likeness properties. Conclusions: Collectively, this study provides a strong foundation for further research into the development of novel anticancer drugs derived from T. macrophylla leaves, targeting breast cancer and melanoma.
Taslima Begum, Muhammad Akmal Hakim Ab Rahim, S. A. A. Shah et al.· The Journal of pharmacy· 0 citations
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