Introduction. Some cytostatic drugs are based on the compounds of plant origin. Development of the new plant metabolites-derived antitumor drugs is an actual and perspective trend in oncology. Recently we isolated a compound from the rhizome of Petasites hybridus (L.) and identified it as a corynan-like indole alkaloid P1.Aim. To identify of the possibility of the Petasites hybridus (L.)-derived alkaloid to bind with molecular targets mediating carcinogenesis and tumor growth and the assessment of its effect on tumor and normal cell cultures.Materials and methods. The research was performed in silico by molecular docking and in vitro by cultural methods. Molecular docking of alkaloid Р1 with receptors of epidermal growth factor (EGFR), platelet growth factor (PDGFR), MET, MRP2 and NOX4 was carried out using software AutoDock Vina 4.0. The docking area grid was built in AutoDockTools 1.5.7. Cultural experiments were performed on tumor cell line highly expressing EGFR (Н1299) and normal lung fibroblasts. Cells were cultured with various concentrations of the alkaloid, their viability was assessed in ХТТ-test and by direct count of alive and dead cells.Results. Maximal binding energy of alkaloid Р1 with molecular targets was noted for МеТ (–8,6 kcal/M), minimal – for NOX4 (–5,9 kcal/M). Binding energy of alkaloid Р1 with EGFR was –6,4; with PDGFR –7,2; with MRP2 –6,3 kcal/M. Binding of alkaloid P1 occurred with the amino acid residues of the active centers of the majority of the studied receptors. Alkaloid showed the ability to inhibit the growth of H1299 cell line (lung adenocarcinoma) in the wide range of concentrations more actively than of normal fibroblasts: half-maximal inhibitory concentration for P1 was 127,24 and 256,29 μM/l respectively. Maximal difference of the dead cells amount between H1299 line and fibroblasts was observed in alkaloid concentrations 21,7–87 μM/l, but, in spite of some signs of mitotic failure (multinucleate and giantnucleate H1299 cells) mitotic index did not change.Conclusion. Alkaloid isolated from the rhizome of Petasites hybridus (L.) is able to bind with the targets mediating tumor growth and impairs lung adenocarcinoma Н1299 cells. Further research is necessary for detailed study of its` antitumor effect in in vitro and in vivo models.

The mechanisms of action of probiotics at the molecular level remain an active subject of discussion and study. It is evident that the bioactive metabolites of probiotic strains exhibit not only antimicrobial and antifungal properties but also more subtle regulatory effects. Of particular interest are the anticancer effects of probiotics, with increasing data accumulating in recent years regarding this area. In this study, we have investigated one such potential mechanism. Bioactive peptides are characteristic of Bacillus strains, known for their probiotic capabilities in veterinary medicine and aquaculture, and were tested for their ability to interact with several key eukaryotic proteins involved in important intracellular signalling pathways. Short peptides such as bacillomycin, fengycin, and others obtained from Bacillus were selected for docking with the targets NOX4, EGFR, PDGFR, and OCTN2. Iturin D showed high binding energy values with NOX4 and PDGFR (−17.996 and −21.11 kcal/mol respectively), while fengycin showed even higher free binding energy with these receptors (−28.21 and −24.51 kcal/mol respectively), indicating its potential binding capability with these key receptors. Furthermore, fengycin was ranked second in binding energy with EGFR and OCTN2 (−21.97 and −24.35 kcal/mol respectively), and plipastatin showed the best results with EGFR (−21.34 kcal/mol) and was second-ranked with NOX4 and OCTN2 (−23.20 and −28.95 kcal/mol respectively).Overall, plipastatin and fengycin exhibited significant activity in binding with all receptors, making them promising candidates for further research as modulators of these receptors.

Bacillus-derived lipopeptides are known to possess diverse biological activities, including antimicrobial and anticancer properties, though the mechanisms of such effects at the molecular level remain incompletely understood. We investigated whether non-ribosomal peptide metabolites from Bacillus can directly interact with transmembrane receptors implicated in oxidative stress regulation and cancer progression (NOX4, EGFR, PDGFR, and OCTN2) using molecular docking and 200 ns molecular dynamics simulations of 11 lipopeptide metabolites. Molecular docking revealed several strong ligand–protein interactions, with plipastatin and fengycin emerging as lead compounds demonstrating the highest binding affinities to multiple receptors. For NOX4, iturin D showed the strongest docking score of −7.85 kcal/mol. Fengycin demonstrated a high docking score of −7.38 kcal/mol for PDGFR and −8.1 kcal/mol for EGFR. Plipastatin showed the strongest docking scores of −11.12 kcal/mol for EGFR and −8.7 kcal/mol for OCTN2. Molecular dynamics simulations confirmed complex stability for these lead compounds, with protein RMSD remaining stable at ~1.5 Å and ligand RMSD between 1.9 and 6 Å over 200 ns. Our findings suggest that plipastatin and fengycin may act as modulators of key receptors involved in oxidative stress and cancer-related signaling. However, those in silico predictions require experimental validation. This work provides the first computational evidence of potential lipopeptide–receptor interactions and establishes a foundation for future experimental investigation of probiotic-derived therapeutics.

Indole-3-propionate (IPA) is a microbiota-dependent metabolite of tryptophan that is attracting attention as a potential component for modulating the tumor microenvironment and enhancing antitumor therapy. Objective. To analyze current data on the biosynthesis of IPA by the gut microbiota and its influence on cellular processes associated with carcinogenesis, including apoptosis, proliferation, and inflammation. Materials and methods. A literature search was carried out in the Google Scholar and PubMed databases without time restrictions, using keywords in Russian and English: «indole-3-propionate», «cancer», «oncology», «IPA». Results. Based on the performed analysis, we structured the review into several subsections to provide a comprehensive assessment of the effect of IPA on tumor cells. Particular attention is paid to the molecular mechanisms of IPA action, such as activation of antioxidant pathways and regulation of AhR, PI3K/Akt, and NF-κB signaling cascades. The study presents the results of preclinical research using cancer models of various nosologies, identifies the potential for IPA application as a component of combination therapy, and outlines key directions for future research. Conclusion. It has been shown that IPA is a promising bacterial metabolite for developing new strategies for antitumor therapy. Key areas for further research include optimizing IPA delivery regimens, investigating its efficacy in combination with existing treatment methods, and performing clinical trials.