Insights into Molecular Mechanisms of Polyphenolic Compounds from Helichrysum italicum by Inverse Molecular Docking Fingerprint Approach
Year: 2026
Type: article
Abstract: Background/Objectives: Natural compounds occupy a pharmacologically rich chemical space, characterized by abundant scaffolds, extensive functional group elaboration, and defined stereochemistry. In this context, Helichrysum italicum, a Mediterranean medicinal plant, represents a valuable source of polyphenols with multiple biological and pharmacological activities. Methods: Here, we introduce an inverse molecular docking fingerprint approach to systematically investigate eight major Helichrysum italicum polyphenols, including α-pyrones (arzanol, ethylpyrone), flavonols (gnaphaliin, kaempferol, quercetin), and flavanones (naringenin, pinocembrin, hesperetin). More than 40,000 human protein structures from the Protein Data Bank were screened to generate target-based inverse docking score fingerprints for each compound. Results: Hierarchical clustering of these fingerprints revealed shared binding patterns among structurally related polyphenols and enabled hypothesis generation regarding potential synergistic effects. Notably, favorable interactions were identified with PPARG and CARM1, supporting therapeutic relevance in inflammation and cancer, alongside additional targets associated with neurodegeneration and bone metabolism. Conclusions: This study establishes inverse docking fingerprints as a robust, mechanism-oriented method for natural product research and highlights Helichrysum italicum polyphenols as starting points for medicinal chemistry and drug discovery.
Source: Pharmaceuticals
DOI: 10.3390/ph19040647
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: Computer-aided framework for the systematic synthesis, design, and integration of flow chemistry and microprocesses into sustainable production systems targeting Power-to-X, BBMRI, Multi-omic analysis of NFkB-mediated signaling in multiple sclerosis, Unlocking the Selective Catalytic Conversion Processes of CO2 to Ethanol – UliSess, Chemical Carcinogenesis and Neurodegeneration: Molecular-Level Mechanistic Impact of Microwave Irradiation, Optical Chemical/Bio Sensor Systems (OPTISENS), Production, Isolation and Formulation of Health Beneficial Substances from Helichrysum Italicum for Applications in Cosmetic Industry, Computationally intensive complex systems, Unveiling the Analgesic Potential of Herkinorin: A Comprehensive Approach to Designing Safer Opioids, Mechanistic insights into the anticarcinogenic, antioxidative, and antimicrobial activity of natural polyphenolic compounds from Helichrysum italicum, Non-invasive multi-omics biomarkers in immune cells subtypes for personalized medicine in childhood asthma and molecular mechanisms of non-response to inhaled corticosteroids, Library of opioid binding patterns in correlation with their adverse side effects, Coronaviral therapeutic target mutagenesis platform for communal treatment evaluation and the development of pan-coronavirus inhibitors, Development of Electrochemical Biosensor for Detection of Methylmercury, ProBiS-Fold approach for binding site detection for whole structural human proteome in drug discovery, Artificial Intelligence for Science
OpenAlex ID: W7155073776