HER2 (human epidermal growth factor receptor 2) is a critical oncogenic driver in aggressive breast cancers (BC) and remains an important target for therapeutic intervention. Although targeted therapies such as trastuzumab deruxtecan have shown remarkable efficacy, identifying alternative HER2 inhibitors is essential to overcome resistance and expand treatment options. In this study, an integrated in-silico drug repurposing strategy combining pharmacophore-based virtual screening of the DrugBank database, molecular docking, prime Molecular Mechanics Generalized Born Surface Area (MM/GBSA), molecular dynamics (MD) simulations, and post-MD MM/GBSA free energy calculations was applied to identify FDA-approved compounds with potential HER2+ inhibitory activity. The SwissSimilarity screening of the DrugBank database using the pharmacophore-based screening method retrieved fourteen (14) compounds structurally similar to trastuzumab deruxtecan, with similarity scores between 0.352 and 0.751. Further, molecular docking performed using PyRx revealed strong binding affinities ranging from -7.9 to -11.6 kcal/mol, identifying Exatecan (-11.6 kcal/mol), Gimatecan (-10.9 kcal/mol), and Lurtotecan (-10.6 kcal/mol) as top candidates. The clinically approved HER2-targeted drug Trastuzumab Deruxtecan was used as a reference compound for benchmarking the binding interactions, exhibiting a binding affinity of -9.9 kcal/mol. Moreover, prime MM/GBSA calculations supported these findings, with binding free energies of -53.00 kcal/mol for trastuzumab deruxtecan and -45.84 kcal/mol for lurtotecan. MD simulations over 200 ns confirmed the conformational stability of the Lurtotecan-HER2 complex, demonstrating consistent root-mean-square deviation (RMSD) and root-mean-square fluctuations (RMSF) profiles, a stable radius of gyration (RoG), and hydrogen bonding (HB), indicating enhanced structural compactness. Post-MD simulation MM/GBSA analysis revealed a binding free energy of -26.13 ± 8.50 kcal/mol for Lurtotecan, which was comparable to -24.18 ± 6.21 kcal/mol for Trastuzumab Deruxtecan, indicating stable interactions with HER2. Functional enrichment analysis (GO and KEGG) revealed a significant association with oncogenic pathways such as “Pathways in cancer” (hsa05200), involving HER2, PIK3CA, and MTOR. Collectively, these integrative computational findings highlight lurtotecan as a promising candidate for repurposing against HER2+ BC and merit further in vitro and in vivo evaluation.

The therapeutic potential of psilocybin in treating psychiatric disorders has gained attention recently. While most research has focused on isolated psilocybin, evidence suggests that whole mushroom extracts exhibit greater efficacy, implicating a possible entourage effect of additional bioactive compounds. This study aimed to elucidate the holistic neuropharmacological effects of psilocybin-producing mushroom compounds through a computational framework incorporating network pharmacology, molecular docking, and molecular dynamics. Fifteen mushroom-derived compounds were identified from literature, of which eight exhibited favorable pharmacokinetic profiles. Target prediction and network analysis identified 44 brain-localized proteins with partial biological connectivity. Functional enrichment and pathway analyses implicate key neurological pathways. The compounds exhibited strong docking scores to neurologically relevant targets. Several compounds formed stable salt bridges with the Asp155 residue of HTR2A, mirroring serotonin’s binding behavior. Molecular dynamics simulations further confirmed high residence stability of the compounds within the binding pockets of HTR2A and MAOA. These findings support a mechanistic rationale for the enhanced efficacy of whole mushroom extracts over isolated psilocybin and underscore the therapeutic potential of other constituent compounds. The study highlights the importance of multi-target interactions in mediating neuropsychiatric effects and provides a foundation for further investigations into the synergistic roles of these compounds in CNS modulation.

The anthraquinone, 3-acetyl-2,8-dihydroxy-6-methoxyanthraquinone (1), alongside three naphtoquinones, 8-O-methylbostrycoidin (2), 5-O-methyljavanicin (3), 8-O-methylfusarubin (4), and one alcohol, 2-methylpropane-1,3-diol (5), were isolated from the ethyl acetate extract of the coprophilous fungus, Paecilomyces niveus. The complete NMR data of compound 1 are reported here for the first time, while bostrycoidin, javanicin, and fusarubin-related quinones are described for the first time within the genus Paecilomyces. Structures were elucidated by comprehensive spectroscopic analyses and high-resolution mass spectrometry, as well as by comparison with reported data. Antibacterial activity was assessed by microdilution assays, and the tested compounds exhibited weak activity with MIC values ranging from 781 to 5551 mu M against Staphylococcus aureus, Shigella flexneri, Klebsiella pneumoniae, Salmonella typhimurium, and Escherichia coli. The chemophenetic relevance of the isolates is discussed.

Colon cancer (CC) is a major global health concern, accounting for approximately 930,000 deaths in 2020. Chronic intestinal inflammation contributes to CC development by promoting genetic instability, dysregulated signaling, and malignant transformation of colonic epithelial cells. In this study, we explored natural Usnic Acid (UA) derivatives as potential modulators of inflammation-associated pathways in CC using in-silico approaches. A combination of molecular docking, molecular dynamics (MD) simulations, principal component analysis (PCA), Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculations, and network pharmacology analyses was applied. Among the screened derivatives, Usimine A (USA) exhibited the highest predicted binding affinity (-6.20 kcal/mol) relative to the reference compound 5-Fluorouracil (-5.13 kcal/mol), forming stable interactions with key residues, including a hydrogen bond with Ser530 and a C-H bond with Ser353. MD simulations indicated stable protein-ligand interactions for USA, supported by analyses of RMSD, RMSF, radius of gyration, solvent-accessible surface area, PCA, and dynamic cross-correlation. MM/GBSA analysis predicted a favorable binding free energy for USA (-59.97 ± 5.84 kcal/mol) compared to 5-Fluorouracil (-14.21 ± 1.67 kcal/mol). Network pharmacology and pathway enrichment (GO and KEGG) analyses identified multiple inflammation- and cancer-related pathways, with the HIF-1 signaling pathway (hsa04066) prominently highlighted. This pathway serves as a key regulator linking cellular hypoxia to inflammatory responses and may underlie USA's potential anti-inflammatory effects. These computational results provide mechanistic insights into UA derivatives and suggest candidates for further experimental evaluation in inflammation-associated CC.

Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, emphasizing the urgent need for novel therapeutic agents with improved efficacy. Benzimidazole derivatives possess diverse pharmacological properties, including anticancer, antimicrobial, anti-inflammatory, and antioxidant activities; however, their precise mechanisms against LC remain unclear. In this study, an integrative in-silico approach combining network pharmacology (NP), molecular docking, molecular dynamics (MD) simulations and molecular mechanics/generalized born surface area (MM/GBSA) were employed to elucidate the potential mechanisms of benzimidazole derivatives against LC. NP analysis identified key molecular targets associated with LC, while molecular docking with the best target Cyclin-Dependent Kinase 4 (CDK4) revealed that the metal-based benzimidazole derivative CuL1Br exhibited the binding affinity of -7.8 kcal/mol, which is comparable to the control compound Trilaciclib (-8.5 kcal/mol). MD simulations demonstrated the stability and compactness of the CuL1Br-CDK4 complex, with a root mean square deviation (RMSD) of 1.82 ± 0.25 Å, root mean square fluctuation (RMSF) of 1.03 ± 0.64 Å, radius of gyration (RoG) of 19.90 ± 0.12 Å, solvent-accessible surface area (SASA) of 14,562.82 ± 309.24 Ų, and hydrogen bonds (HB) of 136.18 ± 7.67. In comparison, the control complex showed RMSD = 2.02 ± 0.19 Å, RMSF = 1.02 ± 0.63 Å, RoG = 19.99 ± 0.13 Å, SASA = 14,631.79 ± 296.50 Ų, and HB = 132.31 ± 7.60, indicating that CuL1Br binding reduces structural fluctuations and enhances complex stability. Furthermore, principal component analysis (PCA), free energy landscape (FEL), and dynamic cross-correlation matrix (DCCM) analyses corroborate the stable and coordinated motions of the complex over the 200 ns trajectory. Additionally, MM/GBSA calculations showed favorable binding free energy (-17.70 ± 4.82 kcal/mol), reflecting comparable and stable interactions. The favorable ADME characteristics of CuL1Br highlight its promising drug-like profile and support its potential for further pharmacological investigation. Collectively, these results highlight CuL1Br as a promising CDK4 inhibitor with significant therapeutic potential against LC, providing a foundation for further experimental validation and targeted therapy development.

Tuberculosis is one of the world’s most infectious killers, and the rate at which resistance to available medication develops is alarming. Targeting the ATP synthase of Mycobacterium tuberculosis as a strategy to kill the bacteria therapeutically has gained traction. Currently, bedaquiline is used as the cornerstone to treat TB; however, the emergence of resistance to this drug has been reported. This underscores the need to develop novel therapeutic agents. In this study, we employed computational techniques through molecular docking, MMPBSA ranking, DFT, and molecular dynamics simulation to screen phytochemicals from Indian medicinal plants for potential ATP synthase inhibitors. Isoverticine and convallamarogenin were identified based on their good docking scores and total free binding energies (-29.27 Kcal/mol and − 28.37 Kcal/mol, respectively). These compounds were shown to possess good reactivity features from DFT studies. They exhibited similar interaction patterns to bedaquiline, characterized by uniquely strong hydrogen and salt bridge interactions with GLU65 of the subunit C in the Fo region. They also exhibited good druglikeness with minimal interference with metabolic enzymes and possessed good toxicity profiles. Molecular dynamics showed the compounds stabilized within the binding site with resultant reduction in the residual fluctuations of the subunit C. In conclusion, isoverticine and convallamarogenin could serve as lead compounds in the development of anti-TB agents.

Background/Objectives: Diabetes is a chronic metabolic disorder that leads to elevated blood sugar levels and has become a global concern. Though there has been an increase and evolution of antidiabetic drugs and therapeutics, they fall short of the desired efficacy and are often associated with adverse effects. This study explores reduced chalcone as a scaffold to design and synthesize potential antidiabetic drugs with improved efficacy through glycosylation and supplemented by in silico evaluation. Methodology: The 3ʹ-hydroxychalcone was initially reduced to 1-phenyl-3-(3ʹ-hydroxyphenyl)propane (2), followed by direct C-glycosylation at C-4ʹ under temperature control from -78 ℃ to room temperature (RT) and afforded the C-4ʹ glucosylated 1,3-diaryl propane. The first step in the mechanism was 3ʹ-O-glycosylation, and the resultant 3ʹ-O-a,b-glucose isomer mixture was isolated at -40 ℃. NMR spectroscopy and mass spectrometry were used to characterise and validate compound structures. These compounds' antidiabetic potentials and drug-likeness were evaluated through integrated computational techniques. Results: The main compound (5) showed no inhibitory activity against α-glucosidase and α-amylase. However, all the compounds showed higher probable antidiabetic activities and improved drug-likeness relative to aspalathin. Their binding affinity assessment showed they are potential ‘pan-binders’ with high binding affinities to several proteins implicated in the advancement of diabetes, including AKT, AMPK, GLUT4, SGLT2, and SIRT6. Furthermore, they were observed to stabilise within the binding pocket of AKT, underscored by strong hydrogen and hydrophobic bonds resulting in protein conformational changes, thus highlighting their antidiabetic potential. Conclusion: The synthesised glucosyl chalcones could be potential lead compounds for developing novel antidiabetic compounds.

Liver cancer (LC) is the fourth most prevalent cause of cancer-related death worldwide. However, existing treatment options have limitations, as they do not consistently provide benefits to all patients. With an emphasis on pyrimidine derivatives, this study uses virtual screening approaches to find possible therapeutic agents against LC. These techniques include ADMET prediction, molecular docking, molecular dynamics (MD) simulations, density functional theory (DFT), and network pharmacology analysis. Fifteen compounds (1, 4, 6, 9, 16, 18, 27, 33, 38, 39, 40, 43, 44, 49, and 50) were selected for molecular docking studies against the EGFR kinase mutant T790M/L858R (PDB ID: 3W2Q) based on their favorable drug-like properties as determined by ADMET analysis. Compound 9 had the best Prime MM/GBSA score of -51.55 kcal/mol and the strongest binding affinity of -7.9 kcal/mol among the compounds that were chosen. It formed several hydrogen bonds with significant residues, including Lys745, Thr854, Met793, and Gln791, in the active site of the EGFR kinase mutant T790M/L858R. These interactions were superior to those of the reference compound (Erlotinib), which had a binding affinity of -6.4 kcal/mol and an MM/GBSA score of -52.51 kcal/mol. The enhanced stability of compound-9 over Erlotinib and the apo protein was also confirmed by molecular dynamics (MD) simulations, as evidenced by significant parameters such as RMSD, RMSF, radius of gyration (RoG), hydrogen bond interactions, principal component analysis (PCA), dynamic cross-correlation matrix (DCCM), and free energy landscape (FEL) analysis. Furthermore, the binding free energy of compound-9 was − 39.62 kcal/mol, while that of Erlotinib was − 42.13 kcal/mol. Network pharmacology research identified EGFR as a key target in the development of liver cancer (LC), since Gene Ontology (GO) and KEGG enrichment studies indicate that compound-9 may exert its inhibitory effects through several pathways, including the EGFR kinase pathway. These findings highlight the potential of compound-9 as a drug to treat LC.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, marked by hyperinsulinemia, hyperandrogenism, menstrual irregularities, and long-term metabolic complications. Cytochrome P450 17A1 (CYP17A1) is a key enzyme in the biosynthesis of adrenal and gonadal steroids, and its overexpression leads to enhanced conversion of androgens into testosterone, contributing to hyperandrogenism. Targeting CYP17A1 activity presents a viable strategy to mitigate androgen production in the ovaries. In this study, sulfonamide-based antidiabetic drugs were evaluated through molecular docking to identify potential CYP17A1 inhibitors. Among the candidates, Chlorpropamide and Tolazamide demonstrated notable binding affinities and prime MM/GBSA energies of − 5.04, − 16.07 and − 5.79, − 14.90 kcal/mol, respectively, compared to the reference compound Clomiphene (–7.59, − 14.62 kcal/mol). Molecular dynamics (MD) simulations further validated the enhanced stability of the Chlorpropamide and Tolazamide complexes over the apo form and the reference compound, supported by RMSD, RMSF, RoG, SASA, PCA, and DCCM analyses. Post-MD MM/GBSA binding energy calculations confirmed favorable interactions, with Chlorpropamide and Tolazamide showing − 37.03 ± 3.55 and − 27.82 ± 3.40 kcal/mol, respectively, while Clomiphene showed − 45.16 ± 5.96 kcal/mol. Furthermore, ADME profiling using SwissADME revealed that both Chlorpropamide and Tolazamide possess favorable pharmacokinetic and drug-likeness properties, including high gastrointestinal absorption, good bioavailability scores, and compliance with major drug-likeness filters, supporting their potential as viable therapeutic agents. These results highlight the potential of Chlorpropamide and Tolazamide as promising therapeutic agents for PCOS management.

This study investigated the suitability of three as yet undescribed Ochna rhizomatosa biflavonoids, 2,3-dihydroochnaflavone-7'',7-O-dimethylether (compound 1), 7,4'-dihydroxyflavonol-[(C(3')-O-C(4')]-7-hydroxyflavonol (compound 2) and 7-O-methylkaempferol-[C-3 '(I)-O-C-3 '(II)]-luteolin (compound 3), against drugresistant Plasmodium falciparum, the most virulent human malarial parasite. Increase in resistance to available drugs warrants the need to search for new potent agents. Here we interacted compounds 1, 2, 3 and other isolates with the receptor protein (6YCX) responsible for P. falciparum survival and virulence, using the molecular docking approach. We employed FT-IR, NMR (1H and 13C), HR-ESIMS, UV-visible spectroscopy, biological activity and geometrical analysis, while electronic computations were performed using DFT/B3LYP6-31+G(2d,2p) level of theory. Result shows that compounds 1 (0.72 mu M) and 3 (4.60 mu M) exhibited promising antiplasmodial activity than the rest of the isolates which is largely attributed to the presence of methoxy groups at C7' atoms. Frontier molecular orbital (FMO) analysis result shows that compounds 1 and 3 are better chelating agents, forming stable complexes with much better electrophilic and nucleophilic interactions than compounds 2, 4, and 5. Molecular docking results reveal that compounds 1, 2, 3 and 5 exhibit stronger binding affinities and contains higher conventional hydrogen bonding contributed by specific amino acid residues at the active site of 6YCX than the standard drugs; -10.0 kcal/mol, -9.4 kcal/mol, -9.8 kcal/mol, and -9.1 kcal/mol for compounds 1, 2, 3, and 5 respectively while artesunate and chloroquine had -8.7 kcal/mol and -5.7 kcal/mol respectively. This study contributes favorably to the ongoing quest for new drugs against devastating drug-resistant P. falciparum malaria parasite.

One of the most common cancers that kill cancer patients globally is colon cancer (CC), a malignant tumor of the gastrointestinal system. Most anti‐cancer medications on the market today have serious adverse effects, and prolonged use of these medications can result in issues including multidrug resistance and reduced drug absorption, which raises the risk of cancer recurrence. Therefore, the main goal of this research was to discover anti‐CC against threonine tyrosine kinase (TTK) kinase from the authorized drug library utilizing in silico methods, including molecular docking, molecular dynamic (MD) simulation, MM/GBSA, and principal component analysis (PCA) techniques. Luvixasertib is a TTK inhibitor, and the therapeutic agents of Luvixasertib analogues from the approved drug library were tested for their ability to inhibit TTK. According to the molecular docking results, two drugs (Elbasvir and Venetoclax) were shown to be potent TTK inhibitors when compared to the binding energy of Luvixasertib (−8.8 kcal/mol). Elbasvir and Venetoclax showed binding energies of −8.9 and −9.4 kcal/mol, as well as binding free energies of −76.51 ± 5.95 and −59.39 ± 6.07 kcal/mol, respectively. Furthermore, MD simulation trajectories were analyzed using several parameters, including RMSD, RMSF, RoG, SASA, and HB, and based on the results, we determined that Elbasvir and Venetoclax appear to be interesting potential TTK inhibitors. In vitro, in vivo, and clinical studies of Elbasvir and Venetoclax may open the door to their potential use in the prevention of CC.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by sustained hyperglycemia caused by impaired insulin secretion, insulin resistance, or both. Although drugs such as metformin, acarbose, and linagliptin are widely prescribed, their therapeutic performance is often constrained by gastrointestinal side effects and inadequate glycemic control. To address this limitation, thirteen novel imidazole-phenazine derivatives (IPDs) were examined as potential alpha-glucosidase inhibitors using integrated in-silico approaches. Molecular docking results indicated that compound-6 (-10.2 kcal/mol) and compound-9 (-9.8 kcal/mol) displayed stronger binding affinities than the reference drug voglibose (-7.6 kcal/mol), forming stable hydrogen bonds with key catalytic residues Asp214, Glu276, and Asp349. Binding free energy calculations (MM/GBSA) further supported these findings, with Delta Gbind values of -63.4 and -61.7 kcal/mol for compound-6 and compound-9, respectively, compared to -49.2 kcal/mol for voglibose. Molecular dynamics simulations (100 ns) confirmed the structural stability of these complexes, maintaining RMSD within 2.1-2.4 & Aring; and stable hydrogen-bond interactions. Additionally, density functional theory (DFT) analysis revealed lower band gaps (1.24 and 1.69 eV) and higher softness and electrophilicity than voglibose, indicating favorable electronic reactivity. Collectively, these results suggest that compound-6 and compound-9 are promising alpha-glucosidase inhibitor candidates, meriting further in-vitro and in-vivo validation for T2DM therapy.

Tarenna conferta Benth is traditionally used to treat fever, headaches, parasitic and skin diseases. The aim of this study was to identify potential antileishmanial bioactive compounds from T. conferta and in silico studies against target receptors (2JK6 and 2W0H). The performance of successive chromatographic techniques followed by characterization using NMR (1D and 2D) as well as HR-ESIMS analyses, of methylene choride fraction of the stems of T. conferta, led to the identification of two unprecedented derivatives i.e. a new derivative of a dicarboxylic acid (1) and a new hydroxy ester derivative (2), with seven known compounds 3, 4, 5, 6, 7, 8 and 9. Compounds 1, 3 and 4 displayed highly potent antileishmanial activity against Leishmania donovani promastigotes with IC50 values of 3.586 f 0.554 mu g/mL, 0.154 f 0.8123 mu g/mL and 0.789 f 0.105 mu g/mL respectively, compared to amphotericine B (IC50 = 0.198 f 0.704 mu M), used as positive control. However crude extract exhibited significant antileishmanial activity against L. donovani (MHOM/SD/62/1S) promastigotes (IC50 56.860 f 1.755 mu g/mL) and showed no cytotoxicity on RAW 264.7 macrophage cells. The molecular docking provides a captivating glimpse into the intricate interactions between compounds 1, 2, 3, and 4 and the target receptors (2JK6 and 2W0H). The results revealed that, compounds 1, 3, and 4 consistently displayed strong binding affinities and hydrogen bond interactions, showcasing their potential for effective therapeutic interventions. Compounds 2 and 3 exhibit moderate binding affinities with essential amino acids. In terms of potential drug development, compound 4 emerges as a standout candidate due to its exceptionally high binding affinities and specific interactions.

Diabetes mellitus (DM) is one of the most common long-term metabolic illnesses with detrimental implications on health and 90–95

Breast cancer is the most common disease in the world, with about 2 million new cases reported in 2018. It also accounts for 6.6

The pathogenesis of Alzheimer's disease (AD) is complex, involving multiple interrelated pathways. Consequently, developing multi-target-directed ligands may represent an effective therapeutic strategy. This study investigates the anti-Alzheimer potential of two biflavonoids isolated from Allanblackia floribunda against monoamine oxidase A (MAO-A), β-secretase (BACE-1), and glycogen synthase kinase-3β (GSK-3β), three key enzymes implicated in AD progression. The biflavonoids, (2S,3S)-volkensiflavone-7-O-β-glucopyranoside (1) and (2R,3S)-volkensiflavone-7-O-β-D-acetylglucopyranoside (2), were purified and structurally identified using spectroscopic methods. Enzymatic fluorimetric assays were conducted to assess their inhibition of MAO-A, BACE-1, and GSK-3β. The mode and reversibility of inhibition were characterized for both compounds, confirming them as potent MAO-A inhibitors. In silico simulations were performed on the three enzymes to gain insights into their interactions and modes of action. Compounds 1 and 2 were found to be reversible and moderately selective MAO-A inhibitors with IC50 of 35.85 ± 0.03 μM and 25.54 ± 0.05 μM, respectively. These compounds strongly inhibited BACE1 (IC50 = 2.48 ± 0.11 μM and 2.50 ± 0.17 μM, respectively) and GSK-3β (IC50 = 9.39 ± 0.06 μM and 7.17 ± 0.09 μM, respectively). In conclusion, this study is the first to report these compounds as triple inhibitors of MAO-A, BACE-1, and GSK-3β, offering a promising new therapeutic strategy for AD. Molecular docking simulations supported the observed interactions, reinforcing the selective potential of these inhibitors towards target enzymes. The lack of ethnobotanical precedent regarding the use of A. floribunda for managing neurological conditions highlights the novelty of the current study, which reveals, for the first time, the anti-Alzheimer activity of biflavonoids derived from this plant. This underscores the value of scientific investigation in uncovering previously unknown pharmacological properties of traditionally used plants.

This study aimed to investigate the glycaemic control potential and modulation of GABA-induced chloride currents (IGABA) of H. revolutum and the possible bioactive xanthones. Fractions from the leaf and stem extracts (dichloromethane and methanol) were assessed for in vitro α-glucosidase-inhibitory potential and their ability to modulate IGABA (GABAergic effect) through GABAA receptors heterologously expressed in Xenopus oocytes. Xanthones 4-hydroxy-2,3-dimethoxy-9H-xanthen-9-one (1), 3-hydroxy-2,4-dimethoxy-9H-xanthen-9-one (2) and trans-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-5-methoxy-2,3-dihydro-7H-[1,4]dioxino[2,3-c]xanthen-7-one (3) were isolated from the stem and tested in the GABAA receptors assay, but only 3 was assessed for α-glucosidase-inhibitory action. Compared to acarbose (IC50 = 6.16 µM), 3 showed a mild to moderate α-glucosidase-inhibitory activity (IC50 = 45.1 µM), which may be attributed to the absence of a hydroxyl group at its xanthone core. Isomeric compounds 1 and 2 significantly enhanced IGABA with similar efficacy, while 3 was inactive, which may be attributed to its notable structural difference (cyclic ether substitution) compared to compounds 1 and 2. H. revolutum stem contains xanthones with α-glucosidase-inhibitory potential, which also enhance IGABA and could be further studied as a medicinal plant for managing GABAA receptor-mediated mental disorders and/or diabetes.

This study aimed to isolate and characterize bioactive compounds from the roots of Garcinia atroviridis and evaluate their potential anticancer activity, particularly against breast cancer (BC), through network pharmacology and in-silico approaches. Compounds were isolated from the ethyl acetate (EtOAc) extract of G. atroviridis roots using chromatographic and spectroscopic techniques. Their anticancer potential was assessed through network pharmacology analyses, including target prediction, protein–protein interaction (PPI) network construction, and enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Molecular docking and 150-nanosecond molecular dynamics (MD) simulations were conducted to evaluate the binding affinity and stability of compound-target interactions. Five phenolic compounds, namely atrovirisidone, 1,3,5-trihydroxy-2-methoxyxanthone, GB1a, volkensiflavone, and morelloflavone, were successfully identified. Network analyses highlighted HIF1A, ITGB1, RET, HDAC2, and MAPK1 as key molecular targets. GO and KEGG analyses revealed that these targets are associated with cancer-related pathways. All compounds demonstrated strong binding affinities to HIF1A, with docking energies ranging from − 33.02 to − 51.19 kcal/mol, outperforming standard ligands. Among them, morelloflavone exhibited the strongest interaction and stable binding, as confirmed by MD simulations. The phenolic compounds from G. atroviridis, particularly morelloflavone, exhibit significant potential as anticancer agents by modulating HIF1A-related pathways. These findings support further investigation of morelloflavone as a lead compound for breast cancer therapeutics.

Nanodiamonds (NDs) are used more frequently as drug carriers through absorption or chemical modification. In this report, we describe the chemical binding of metal beta-diketonato complexes onto the ND surface using an aminosilane linker. The metals used were iron(III) and copper(II), with beta-diketones, acetylacetone, trifluoroacetylacetone, and the naturally occurring curcumin, which is known for its biological activity. Improved cytotoxicity was observed with metal complexes bound to the drug carrier compared to the free metal complexes as a result of increased stability when bound to a carrier. The curcumin-containing copper(II) conjugate demonstrated an IC50 of 1.85 mu M against the HeLa cell line and showed no toxicity in a larval zebrafish bioassay.