Phloroglucinol Derivatives in Medicinal Applications

Phloroglucinol derivatives, based on the 1,3,5-trihydroxybenzene scaffold, represent a versatile class of natural and synthetic compounds with diverse therapeutic potential. Found predominantly in ferns of the Dryopteris genus and other medicinal plants, these molecules range from simple monomers to complex oligomers and prenylated analogues. Their pharmacological repertoire encompasses antiviral, antibacterial, antifungal, anti-inflammatory, antiplatelet, enzyme-inhibitory and anticancer activities. Mechanistic studies reveal that phloroglucinol cores can interact with key biological targets—such as digestive and bacterial enzymes, viral neuraminidases and signalling kinases—by hydrogen bonding and hydrophobic contacts, often characterised through molecular docking and kinetic analyses. Synthetic modification, including acylation and introduction of allylamine pharmacophores, has increased potency and selectivity against dermatophytes and pathogenic bacteria. In metabolic disorders, certain oligomeric phloroglucinols inhibit glycosidases and glucuronidases, offering novel routes to manage diabetes and drug-detoxification pathways. Moreover, some derivatives suppress osteoclast differentiation and platelet aggregation, indicating applications in bone preservation and cardiovascular health. The global significance of these compounds lies in their potential to address antibiotic resistance, inflammatory diseases and metabolic syndromes, while serving as lead structures for rational drug design and industrial production of high-value pharmaceuticals.

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Phloroglucinol Derivatives in Medicinal Applications publication trend

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Technical terms

Phloroglucinol: A benzene ring bearing three hydroxyl groups at positions 1, 3 and 5; the core unit for a variety of bioactive derivatives.

Dimeric and trimeric phloroglucinols: Oligomeric assemblies of phloroglucinol units linked by carbon–carbon or ether bonds, often exhibiting enhanced potency and target specificity compared with monomers.

β-Glucuronidase: A hydrolase enzyme that cleaves glucuronic acid conjugates, relevant in drug metabolism and detoxification pathways.

Minimum inhibitory concentration (MIC): The lowest concentration of an antimicrobial agent required to prevent visible growth of a microorganism in vitro.

Molecular docking: A computational method for predicting the preferred orientation of a small molecule when bound to a target protein, used to infer binding affinity and key interactions.

References

1. Anti-Influenza Virus (H5N1) Activity Screening on the Phloroglucinols from Rhizomes of Dryopteris crassirhizoma. Molecules (2017).
2. Antifungal Agents: Design, Synthesis, Antifungal Activity and Molecular Docking of Phloroglucinol Derivatives. Molecules (2018).
3. Inhibitory Activity of Bioactive Phloroglucinols from the Rhizomes of Dryopteris crassirhizoma on Escherichia coli β-Glucuronidase: Kinetic Analysis and Molecular Docking Studies. Metabolites (2022).
4. Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae). Frontiers in Pharmacology (2022).
5. Antiplatelet Activity of Acylphloroglucinol Derivatives Isolated from Dryopteris crassirhizoma. Molecules (2019).
6. Water Extract of Dryopteris crassirhizoma Attenuates Bone Loss by Suppressing Osteoclast Differentiation and Function. Evidence-based Complementary and Alternative Medicine (2013).