Cancer remains a leading cause of mortality worldwide, with conventional therapies showing limited efficacy and high toxicity. The increasing incidence and therapeutic resistance necessitate alternative strategies. In this regard, phytochemicals have emerged as potential sources of developing safer and novel anti-cancer agents. This study employs a structure-based drug design approach, integrating molecular docking, molecular dynamics (MD) simulations, and in silico profiling, to investigate the anti-cancer potential of metabolites from Curcuma caesia rhizomes. The research targets key cancer-associated proteins, Matrix Metalloproteinase-9 (MMP9) and Glucose-Regulated Protein 78 (GRP78), identified through expression analysis, functional network mapping, and pathway enrichment as critical mediators of cancer progression and metastasis. A comprehensive molecular docking analysis of 101 bioactive compounds from C. caesia rhizomes identified curcumin and bis-demethoxycurcumin as promising candidates, demonstrating high binding affinities and stable interactions with MMP9 and GRP78. MD simulations further validated the stability and robustness of these interactions under dynamic physiological conditions. Pharmacological profiling, including ADMET analysis, Lipinski's rule compliance, and bioactivity scoring, revealed favorable drug-like properties for both compounds, including strong absorption, distribution, low toxicity, and potential therapeutic activities such as enzyme inhibition and nuclear receptor-mediated processes. KEGG pathway enrichment analysis confirmed their involvement in key biological pathways linked to cancer progression, underscoring their therapeutic potential. The findings highlight curcumin and bis-demethoxycurcumin as promising phytochemical candidates for cancer therapy, capable of modulating MMP9 and GRP78 to suppress tumor progression. While these results provide a solid basis for their therapeutic potential, further experimental studies and clinical trials are crucial to confirm their efficacy and safety for human applications.

• MeSH
• Endoplasmic Reticulum Chaperone BiP MeSH
• Curcuma * chemistry   metabolism   MeSH
• Diarylheptanoids pharmacology   MeSH
• Antineoplastic Agents, Phytogenic * pharmacology   chemistry   MeSH
• Curcumin analogs & derivatives   pharmacology   chemistry   MeSH
• Humans MeSH
• Matrix Metalloproteinase 9 * metabolism   chemistry   MeSH
• Neoplasms * drug therapy   metabolism   MeSH
• Drug Discovery * methods   MeSH
• Rhizome * chemistry   metabolism   MeSH
• Heat-Shock Proteins * metabolism   chemistry   MeSH
• Molecular Dynamics Simulation MeSH
• Molecular Docking Simulation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Endoplasmic Reticulum Chaperone BiP MeSH
• demethoxycurcumin MeSH Browser
• Diarylheptanoids MeSH
• Antineoplastic Agents, Phytogenic * MeSH
• HSPA5 protein, human MeSH Browser
• Curcumin MeSH
• Matrix Metalloproteinase 9 * MeSH
• MMP9 protein, human MeSH Browser
• Heat-Shock Proteins * MeSH

Neurodegenerative disorders (NDs) are typically characterized by progressive loss of neuronal function and the deposition of misfolded proteins in the brain and peripheral organs. They are molecularly classified based on the specific proteins involved, underscoring the critical role of protein-processing systems in their pathogenesis. Alpha-synuclein (α-syn) is a neural protein that is crucial in initiating and progressing various NDs by directly or indirectly regulating other ND-associated proteins. Therefore, reducing the α-syn aggregation can be an excellent option for combating ND initiation and progression. This study presents an in silico phytochemical-based approach for discovering novel neuroprotective agents from bioactive compounds of the Lamiaceae family, highlighting the potential of computational methods such as functional networking, pathway enrichment analysis, molecular docking, and simulation in therapeutic discovery. Functional network and enrichment pathway analysis established the direct or indirect involvement of α-syn in various NDs. Furthermore, molecular docking interaction and simulation studies were conducted to screen 85 major bioactive compounds of the Lamiaceae family against the α-syn aggregation. The results showed that five compounds (α-copaene, γ-eudesmol, carnosol, cedryl acetate, and spathulenol) had a high binding affinity towards α-syn with potential inhibitory activity towards its aggregation. MD simulations validated the stability of the molecular interactions determined by molecular docking. In addition, in silico pharmacokinetic analysis underscores their potential as promising drug candidates, demonstrating excellent blood-brain barrier (BBB) permeability, bioactivity, and reduced toxicity. In summary, this study identifies the most suitable compounds for targeting the α-syn aggregation and recommends these compounds as potential therapeutic agents against various NDs, pending further in vitro and in vivo validation.

• Keywords
• MD simulation, functional network analysis, molecular docking, neuroprotective agent, pathway enrichment analysis, phytochemical,
• Publication type
• Journal Article MeSH

Staphylococcus aureus infections present a significant threat to the global healthcare system. The increasing resistance to existing antibiotics and their limited efficacy underscores the urgent need to identify new antibacterial agents with low toxicity to effectively combat various S. aureus infections. Hence, in this study, we have screened T-muurolol for possible interactions with several S. aureus-specific bacterial proteins to establish its potential as an alternative antibacterial agent. Based on its binding affinity and interactions with amino acids, T-muurolol was identified as a potential inhibitor of S. aureus lipase, dihydrofolate reductase, penicillin-binding protein 2a, D-Ala:D-Ala ligase, and ribosome protection proteins tetracycline resistance determinant (RPP TetM), which indicates its potentiality against S. aureus and its multi-drug-resistant strains. Also, T-muurolol exhibited good antioxidant and anti-inflammatory activity by showing strong binding interactions with flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, and cyclooxygenase-2. Consequently, molecular dynamics (MD) simulation and recalculating binding free energies elucidated its binding interaction stability with targeted proteins. Furthermore, quantum chemical structure analysis based on density functional theory (DFT) depicted a higher energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (EHOMO-LUMO) with a lower chemical potential index, and moderate electrophilicity suggests its chemical hardness and stability and less polarizability and reactivity. Additionally, pharmacological parameters based on ADMET, Lipinski's rules, and bioactivity score validated it as a promising drug candidate with high activity toward ion channel modulators, nuclear receptor ligands, and enzyme inhibitors. In conclusion, the current findings suggest T-muurolol as a promising alternative antibacterial agent that might be a potential phytochemical-based drug against S. aureus. This study also suggests further clinical research before human application.

• Keywords
• MD simulation, density functional theory, molecular docking, pharmacokinetics, phytochemicals,
• MeSH
• Anti-Bacterial Agents * pharmacology   chemistry   MeSH
• Antioxidants pharmacology   chemistry   MeSH
• Bacterial Proteins antagonists & inhibitors   metabolism   chemistry   MeSH
• Phytochemicals * pharmacology   chemistry   MeSH
• Humans MeSH
• Drug Discovery * methods   MeSH
• Computer Simulation MeSH
• Molecular Dynamics Simulation MeSH
• Molecular Docking Simulation MeSH
• Staphylococcal Infections drug therapy   microbiology   MeSH
• Staphylococcus aureus * drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Antioxidants MeSH
• Bacterial Proteins MeSH
• Phytochemicals * MeSH