Identification of Bioactive Phytoconstituents from
Michelia champaca
L. Flowers and Their Interactions with CXCR4 and PTEN Targets: A Comprehensive ADMET,Molecular Docking, and Molecular Dynamics Study
Jul 2026· Journal of Computational Biophysics and Chemistry· 0 citations
TL;DR
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.
Abstract
The identification of bioactive phytoconstituents and their molecular interactions with therapeutic targets provides a rational framework for early-stage drug discovery from medicinal plants. The present study investigates the chemical composition of Michelia champaca L. flower extract using GC—MS and evaluates the potential binding affinity of the prioritized compounds against PTEN (PDB ID: 1D5R) and CXCR4 (PDB ID: 3ODU) via a co-crystal validated in silico workflow. GC—MS profiling putatively identified 42 distinct constituents, with a clear predominance of long-chain fatty acids, primarily n-hexadecanoic acid (44.7%) and octadecanoic acid (26.6%). Following Lipinskis rule of five and ADMET filtering, site-specific molecular docking was executed using a protocol verified by native ligand redocking. Against the PTEN phosphatase active site, the minor polar constituent 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl- exhibited the highest predicted structural affinity, with an exceptional docking score of -7.179 kcal/mol, followed by dl-mevalonic acid lactone (-5.553 kcal/mol). For the CXCR4 transmembrane pocket, Cholesta-4,6-dien-3-ol, (3.beta.)- (-5.280 kcal/mol) and acetamide, N-(4-ethoxy-3-hydroxyphenyl)- (-5.156 kcal/mol) showed the strongest predicted binding interactions. A subsequent 100 ns all-atom molecular dynamics simulation and MM-GBSA free energy analysis of the top-ranked PTENcomplex confirmed strong physical and thermodynamic stability, driven by favorable van der Waals (-30.8 to -36.9 kcal/mol) and electrostatic interactions. These 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.
Natural products from fungi are a significant source for drug discovery. This study investigates six previously uncharacterized metabolites isolated from the poisonous mushroom Tricholoma pardinum using an integrated in silico approach to evaluate their therapeutic potential. Pharmacokinetic (ADMET) profiling predicted varied drug-likeness and toxicity profiles, with several compounds showing potential to cross the blood-brain barrier. Molecular docking and MM-GBSA calculations identified compound 1 as a potent inhibitor of Poly [ADP-ribose] polymerase 1 (PARP1), with a strong binding affinity (XP GScore: -6.756; ΔGbind: -48.75 kcal/mol). This interaction is anchored by a robust network of hydrogen bonds with key residues, including ASP914, CYS908, and THR866. Similarly, compound 6 emerged as a strong binder to Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma (PIP4K2γ) (XP GScore: -7.705; ΔGbind: -45.94 kcal/mol), with its binding stabilized by extensive hydrophobic interactions complemented by a critical hydrogen bond with the residue Methionine 206 (MET206). Subsequent 100 ns molecular dynamics simulations confirmed the high stability of both protein-ligand complexes, validating the persistence of these key interactions. These computational findings highlight the potential of metabolites from T. pardinum as novel scaffolds for developing anticancer agents targeting PARP1 and PIP4K2γ, warranting further experimental validation.
A. Amin, H. M. Amin, A. R. Hamad et al.· Technology and Health Care· 0 citations
The genus Dendrobium is a rich source of bioactive secondary metabolites, particularly bibenzyl derivatives with substantial pharmacological activities, but Dendrobium stuartii remains an underexplored species. Therefore, this study aimed to investigate the drug discovery potential of D. stuartii through an integrated in silico and experimental method. Four key compounds were prioritized through literature analysis, and the interactions with the epidermal growth factor receptor (EGFR) were evaluated using molecular docking. The chemical profile of the acetone extract was characterized using Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS). Additionally, biological activities were assessed through antibacterial, antibiofilm, and anti-inflammatory assays. Batatasin III had the strongest predicted binding affinity toward EGFR, and the LC-HRMS analysis confirmed the presence of bibenzyl derivative 3,4ʹ-dihydroxy-5,5ʹ-dimethoxybibenzyl (gigantol). The extract provided antibacterial activity, specifically against S. aureus and P. acnes, inhibited biofilm formation during the mid-phase, and produced substantial anti-inflammatory activity, as evidenced by significant inhibition of protein denaturation. The results suggested D. stuartii as a promising underexplored source of bioactive compounds with potential applications in anticancer and anti-infective drug development.
Deni Setiawan, Samsul Hadi, Nur Mahdi et al.· Journal of Applied Pharmaceu...· 0 citations
Diabetes mellitus remains a major global health challenge, encouraging the exploration of natural products as alternative therapeutics. Stelechocarpus burahol (kepel), an ethnobotanically significant Indonesian fruit traditionally consumed for its health benefits, represents a promising source of bioactive compounds. This study aimed to integrate ethnobotanical knowledge with molecular insights by identifying potential antidiabetic compounds using an in silico approach. A total of 66 phytochemical compounds were screened through drug-likeness, ADMET, and biological activity prediction, followed by molecular docking against Dipeptidyl Peptidase-4 (DPP-4) (PDB ID: 6B1E). The docking protocol was validated (RMSD 1.697 Å). Several phenolic compounds showed strong binding affinity, particularly gallocatechol (−8.4 kcal/mol), catechin (−8.2 kcal/mol), and 6-hydroxyluteolin (−8.1 kcal/mol), outperforming the native ligand. These findings highlight the potential of S. burahol as a natural source of DPP-4 inhibitors.
Bintang khoirun Nadzifah, T. Sulistiyowati, P. R. Primandiri et al.· Florea Jurnal Biologi dan Pe...· 0 citations
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.
Md Maruf Khan, Md. Arju Hossain, Md Shahadat Hossain et al.· Computers in Biology and Med...· 0 citations
Neisseria gonorrhoeae remains a leading sexually transmitted pathogen worldwide and poses a public health challenge due to rising antimicrobial resistance. This crisis underscores the need for alternative treatment options. In this study, phenolic acids from Philippine Fabaceae plants were evaluated as potential inhibitors of the NagZ protein, an enzyme essential for bacterial cell wall recycling and survival. A total of 388 Fabaceae species obtained from Co’s Digital Flora of the Philippines were screened based on reported phenolic acid content from existing journals and literature. Among these, 92 species were identified to contain documented phenolic acids, yielding a total of 37 distinct phenolic acids. In silico analyses included molecular docking, drug-likeness, ADMET profiling, and molecular dynamics simulations. Among the candidates, ellagic acid, 3,4-Di-O-caffeoylquinic acid, and 4-caffeoylquinic acid showed the strongest binding and favorable pharmacokinetic properties. These top-performing ligands were derived from: 3,4-di-O-caffeoylquinic acid was identified from the leaf of Cassia fistula, while 4-caffeoylquinic acid was obtained from the leaves of Medicago polymorpha. Ellagic acid was remarkably prevalent, found in the flowers of Caesalpinia pulcherrima, the pods of Parkia speciosa, and more. These findings highlight their potential as lead compounds, supporting further in vitro and in vivo validation against resistant gonorrhea.
Grazel Ann M. Caspillo, Sittie Almiraizah A. Masukat, Cristylou Hearth P. Paladin et al.· International journal of res...· 0 citations
Computer-Aided drug design (CADD) and in silico
methods have become indispensable tools in
contemporary drug development. Molecular docking is
essential for anticipating how bioactive substances will
interact with target proteins, which makes it easier to
find possible medicinal treatments. In this study,
molecular docking analysis was used to assess the antiinflammatory potential of phytocompounds discovered
from Ruellia tuberosa. Cyclooxygenase-1 (COX-1;
PDB ID: 2OYE) and Cyclooxygenase-2 (COX-2; PDB
ID: 6COX), two important enzymes implicated in
inflammation, were docked against a selection of
phytochemicals including n-hexadecanoic acid, phytol,
9,12-octadecadienoic acid, octadecanoic acid and
squalene. The normal reference medication was
diclofenac. AutoDock Vina was used in docking
research to forecast binding affinities and patterns of
interaction between ligands and target proteins. The
selected phytochemicals exhibited favorable binding
affinities toward COX-1 and COX-2.
The compounds with the highest binding affinity were
squalene, octadecanoic acid and 9,12-octadecadienoic
acid. Hydrophobic and hydrogen bonding interactions
within the target proteins' active site residues were the
main factors stabilizing the connections. These results
imply that bioactive substances with strong antiinflammatory potential are present in Ruellia tuberosa.
The findings support further in vitro and in vivo studies
for the development of novel anti-inflammatory agents
and highlight the value of molecular docking as a
prediction tool in drug discovery.
Aswathi C.V. Sreenivasan, Prasanna R. Kovath, T. Angayarkanni· Research journal of chemistr...· 0 citations