Novel β-Cyclodextrin-Based Heptavalent Glycyrrhetinic Acid Conjugates: Synthesis, Characterization, and Anti-Influenza Activity
Résumé
In our continuing efforts toward the design of novel pentacyclic triterpene derivatives as potential anti-influenza virus entry inhibitors, a series of homogeneous heptavalent glycyrrhetinic acid derivatives based on β -cyclodextrin scaffold were designed and synthesized by click chemistry. The structure was unambiguously characterized by NMR, IR, and MALDI-TOF-MS measurements. Seven conjugates showed sufficient inhibitory activity against influenza virus infection based on the cytopathic effect reduction assay with IC 50 values in the micromolar range. The interactions of conjugate 37 , the most potent compound (IC 50 = 2.86 μ M, CC 50 > 100 μ M), with the influenza virus were investigated using the hemagglutination inhibition assay. Moreover, the surface plasmon resonance assay further confirmed that compound 37 bound to the influenza HA protein specifically with a dissociation constant of 5.15 × 10 −7 M. Our results suggest the promising role of β -cyclodextrin as a scaffold for preparing a variety of multivalent compounds as influenza entry inhibitors.
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