Acetylcholinesterase (AChE) holds significance in Alzheimer's disease (AD), where cognitive impairment correlates with insufficient acetylcholine levels. AChE's role involves the breakdown of acetylcholine, moderating cholinergic neuron activity to prevent overstimulation and signal termination. Hence, inhibiting AChE emerges as a potential treatment avenue for AD. A library of 2500 compounds, derived from 25 traditionally used medicinal plants, was constructed using the IMPAAT database of traditional medicinal plants. The canonical SMILES of these compounds were collected and underwent virtual screening based on physicochemical properties, with subsequent determination of IC₅₀ values for the screened compounds followed by analysis using machine learning (ML). Subsequently, a molecular docking study elucidated both binding affinity and interactions between these compounds and AChE. The top three compounds, exhibiting robust binding affinities, underwent MM-GBSA analysis for molecular docking validation, succeeded by pharmacokinetics and toxicity evaluations to gauge safety and efficacy. These three compounds underwent MD simulation studies to assess protein–ligand complex conformational stability. Additionally, Density Functional Theory (DFT) was employed to ascertain HOMO, LUMO, energy gap, and molecular electrostatic potential. Among 2500 compounds, physicochemical properties-based virtual screening identified 80 with good properties, of which 32 showed promising IC₅₀ values. Molecular docking studies of these 32 compounds revealed various binding energies with AChE, with the best three compounds (CID 102267534, CID 15161648, CID 12441) selected for further analysis. MM-GBSA studies confirmed the promising binding energies of these three compounds, validating the molecular docking study. Further, the MD simulation studies have confirmed the structural and conformational stability of these three protein–ligand complexes. Finally, DFT calculations revealed favorable chemical features of these compounds. Thus, we can conclude that these three compounds (CID 102267534, CID 15161648, CID 12441) may inhibit the activity of AChE and can be useful as a treatment for Alzheimer's disease.

Diabetes, characterized by elevated blood sugar levels, poses significant health and economic risks, correlating with complications like cardiovascular disease, kidney failure, and blindness. Dipeptidyl peptidase-4 (DPP-4), also referred to as T-cell activation antigen CD26 (EC 3.4.14.5.), plays a crucial role in glucose metabolism and immune function. Inhibiting DPP-4 was anticipated as a potential new therapy for diabetes. Therefore, identification of plant-based natural inhibitors of DPP-4 would help in eradicating diabetes worldwide. Here, for the identification of the potential natural inhibitors of DPP-4, we developed a phytochemicals library consisting of over 6000 phytochemicals detected in 81 medicinal plants that exhibited anti-diabetic potency. The library has been docked against the target proteins, where isorhamnetin, Benzyl 5-Amino-5-deoxy-2,3-O-isopropyl-alpha-D-mannofuranoside (DTXSID90724586), and 5-Oxo-7-[4-(trifluoromethyl) phenyl]-4H,6H,7H-[1,2]thiazolo[4,5-b]pyridine 3-carboxylic acid (CHEMBL3446108) showed binding affinities of −8.5, −8.3, and −8.3 kcal/mol, respectively. These compounds exhibiting strong interactions with DPP-4 active sites (Glu205, Glu206, Tyr547, Trp629, Ser630, Tyr662, His740) were identified. ADME/T and bioactivity predictions affirmed their pharmacological safety. Density functional theory calculations assessed stability and reactivity, while molecular dynamics simulations demonstrated persistent stability. Analyzing parameters like RMSD, RG, RMSF, SASA, H-bonds, MM-PBSA, and FEL confirmed stable protein–ligand compound formation. Principal component analysis provided structural variation insights. Our findings suggest that those compounds might be possible candidates for developing novel inhibitors targeting DPP-4 for treating diabetes.

Hypoxia is a defining feature of physiological stress and the core of solid tumors, where aberrant vascularization limits oxygen delivery; cells respond through mechanisms that extend beyond the canonical stabilization of hypoxia-inducible factors (HIFs). Recent studies suggest that hypoxia can promote the formation of specific biomolecular conden-sates, membraneless compartments generated through liquid–liquid phase separation in which regulatory proteins and RNAs become locally enriched at genomic regions, while chromatin mainly serves as an organizational scaffold. Transcription factors, the coacti-vators p300/CBP, Mediator, and BRD4, chromatin-modifying enzymes, and architectural RNAs such as NEAT1 and MALAT1 partition into these compartments, and their con-densation can help reorganize local chromatin structure and enhancer–promoter interac-tions. Because molecular oxygen is a shared co-substrate for the Jumonji-C histone demethylases and the ten-eleven translocation (TET) DNA dioxygenases, hypoxia reshapes histone methylation and DNA methylation in parallel, and readers that bridge these marks, including UHRF1, may participate in condensate-associated chromatin regulation. Hypoxia-driven condensation of ZHX2 rewires enhancer–promoter contacts and higher-order genome architecture, influencing cell identity, stemness, and metastatic potential, and Polycomb condensates represent another candidate epigenetic compartment that may be influenced by hypoxic signaling. These processes may be particularly important in cancer, where chronic hypoxia provides a sustained stimulus for condensate formation and epigenetic remodeling. Together, these findings support a model in which phase separation and epigenetic reprogramming are not separate layers but one integrated response to low oxygen, offering opportunities to target maladaptive condensates in disease.