This study investigated the interaction between cannabidiol (CBD) derivatives and the GPR55 receptor using a bioinformatics-driven molecular docking approach. GPR55, implicated in central nervous system (CNS) pathologies, represents a promising target for novel therapeutics. Drug-likeness evaluation via SwissADME confirmed that all selected derivatives complied with Lipinski′s Rule of Five, exhibiting favorable physicochemical properties with molecular weights below 500 Da and acceptable logP values. Molecular docking simulations, performed using AutoDock Vina through PyRx, revealed strong binding affinities, with docking scores ranging from −9.2 to −7.2 kcal/mol, indicating thermodynamically feasible interactions. Visualization and interaction analysis identified a conserved binding pocket involving key residues, including TYR101, PHE102, TYR106, ILE156, PHE169, MET172, TRP177, PRO184, LEU185, LEU270 and MET274. Ligand clustering in this region further supports the presence of a structurally defined binding site. Molecular dynamics simulations of GPR55 in complex with the three top-scoring ligands (3″-HOCBD, THC, and CBL) revealed that all ligands remained stably bound within the cavity over 100 ns, with ligand-specific rearrangements. Predicted oral bioavailability was moderate (0.55), consistent with the need for optimized formulations to enhance systemic absorption. These findings suggest that CBD derivatives may act as potential modulators of GPR55, offering a basis for the development of novel CNS-targeted therapeutics.

Melanoma remains a highly aggressive malignancy, particularly in advanced metastatic stages where therapeutic options are limited. Natural compounds provide a structural basis for discovering novel anticancer agents. In this study, we employed an integrated in silico approach to evaluate the pharmacokinetic properties, toxicity profiles, and molecular targets of key alkaloids from Chelidonium majus, including berberine, sanguinarine, chelerythrine, chelidonine, protopine, umbelliferone and coptisine. ADME/T predictions (SwissADME and DeepPK) revealed favorable drug-likeness and oral bioavailability for most compounds, with berberine exhibiting the most balanced safety and absorption profile. All compounds demonstrated high intestinal absorption (>99%) and implicated key melanoma targets, including APE1/Ref-1, CXCR4, CCR2, TLR8, galectin-3, and VEGFR2. These molecules represent valuable templates for the development of melanoma therapies. Among the tested compounds, chelidonine emerged as a potential APE1 inhibitor, exhibiting the highest binding affinity and forming specific interactions within the enzyme’s catalytic site, suggesting its potential as a DNA repair-targeted agent in melanoma. These findings support the further exploration of natural alkaloids, including structural optimization or advanced formulation strategies, to enhance safety, bioavailability, and therapeutic efficacy in melanoma.

Background/Objectives: Natural plant-based compounds, especially black pepper extract, are known to have anti-inflammatory, antibacterial, and antioxidant qualities that promote procollagen formation and wound healing. This study focused on developing a collagen-based composite enriched with P. nigrum extract in powder form, designed to enhance the efficacy of the antibiotic cefazolin while promoting the healing of chronic wounds. Methods: The polyphenolic P. nigrum extract was obtained by ultrasound-assisted extraction and was characterised by UHPLC-MS/MS and spectrophotometry. Antimicrobial and antioxidant activities were assessed using conventional methods. Pharmacokinetic and pharmacodynamic parameters were evaluated for the specific taxon compounds using Deep-RK. P. nigrum extract was incorporated into a collagen hydrogel with arginine and freeze-dried. The powders were characterised by FTIR, SEM, TGA-DSC, and DLS. The antimicrobial activity and potential synergistic effects with cefazolin were evaluated on reference microbial strains and isolates from infected wounds. Biocompatibility and hemocompatibility were evaluated, as well as wound closure in vitro. Results: Polyphenols, including phenolic acids, stilbenes, anthocyanins, and flavonoids, which provide a potent antioxidant capacity through electron transfer mechanisms (FRAP, CUPRAC), were abundant in the P. nigrum extract. FTIR and SEM analyses confirmed the integration of phenolic compounds into the collagen–arginine matrix without protein denaturation. TGA–DSC data showed thermal stabilisation at moderate extract concentrations. The extract exhibited predominantly bacteriostatic antibacterial activity and antibiofilm effects, with synergy/additivity with cefazolin, especially at medium doses. Tests on keratinocytes confirmed biocompatibility, and hemocompatibility demonstrated an excellent safety profile, with protection against AAPH-induced oxidative stress. Conclusions: Overall, collagen powders with P. nigrum extract at moderate/low concentrations combine stability, antibiotic-enhanced activity, and cellular compatibility, making them promising adjuvants for the topical treatment of chronically infected wounds.

Dermatological pathologies are multifactorial conditions that often show limited response to single-target therapies. Natural compounds may offer advantages through their pleiotropic effects on inflammation, oxidative stress, and tissue repair. This study employed an integrated in silico approach to evaluate selected phytoconstituents from Melaleuca alternifolia, Lavandula angustifolia, Tamarix ramosissima, and Curcuma longa. Drug-likeness, pharmacokinetic properties, dermal permeability, and toxicity were assessed using SwissADME and admetSAR 3.0. SwissTargetPrediction and the Similarity Ensemble Approach (SEA) identified carbonic anhydrases (CAs) among the predicted molecular targets, supporting the selection of CA IV and CA IX for structure-based analysis. Molecular docking identified favorable catalytic-site poses for several compounds, with curcuminoid and flavonoid scaffolds generally showing more favorable predicted affinities. Cyclocurcumin, tamarixetin, and scopoletin were subsequently investigated by molecular dynamics simulations. The simulations revealed scaffold- and isoform-dependent differences in interaction persistence: cyclocurcumin showed pronounced conformational flexibility, tamarixetin displayed more progressive displacement, and scopoletin showed the lowest persistence in the catalytic region. Overall, the results generate testable hypotheses regarding natural compound interactions with CA IV and CA IX, but experimental binding and enzymatic assays are required to establish CA modulation and therapeutic relevance.