20.500.12556/DKUM-97898 Insights into molecular mechanisms of polyphenolic compounds from Helichrysum italicum by inverse molecular docking fingerprint approach 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, aMediterranean 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 Helichrysum italicum polyphenolic compounds protein targets inverse molecular docking fingerprints molecular mechanisms synergistic effects mode of action biological effects laški smilj proteini fenoli sinergijski učinek true false true MDPI Angleški jezik Slovenski jezik https://www.mdpi.com/journal/pharmaceuticals © 2026 by the authors Članek v reviji 2026-04-23 09:06:20 2026-04-23 09:06:21 2026-04-24 03:16:12 0000-00-00 00:00:00 2026 0 0 29 str. iss. 4, [article no.] 647 Vol. 19 2026 0000-00-00 Zaloznikova Objavljeno apc 2026-04-08 2026-04-17 2026-04-21 615.38 276107011 10.3390/ph19040647 1424-8247 pharmaceuticals-19-00647.pdf pharmaceuticals-19-00647.pdf 1 A1B29DCD955F3EF106F6D23FC22A8371 2b246f49d2bba5dd7768bf7ebf0323bd963cdb5ca8605847f611d926a67259ab afaa1235-3ee3-11f1-a8d8-00155d0001a1 https://dk.um.si/Dokument.php?lang=slv&id=205570 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0