Crystalline Liquiritigenin and Liquiritin: Structural Characterization, Molecular Docking Studies, and Anti-Amyloid-β Evaluation in Caenorhabditis elegans

Two new crystalline compounds, named [LG·H₂O] (1; LG = liquiritigenin) and [LQ·C₂H₅OH·H₂O] (2; LQ = liquiritin), have been synthesized and structurally characterized by single-crystal and powder X-ray diffraction, thermogravimetric analyses (TGA), nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and infrared spectra (IR). 1 and 2 crystallize in space groups Pna2₁ and P2₁2₁2₁, respectively. In the structure of 1, liquiritigenin and water molecules are connected by hydrogen bonds for the construction of a novel 3,5-connected network topology with a point symbol of (6³)(6⁷·8³), in which each liquiritigenin and water molecule acts as a 5-connected and 3-connected node, respectively. Both 1 and 2 reduce amyloid-β-induced toxicity in Caenorhabditis elegans (CL4176 strain) by improving the expression level of SOD. Gene expression studies by RT-qPCR indicate upregulation of skn-1 and sod-3 expression while downregulation of daf-16 and hsf-1 expression in C. elegans. Molecular docking studies indicate that LG and LQ combine well with vascular endothelial growth factor A (VEGFA), with free binding energies calculated to be -6.7 and -7.9 kcal·mol^-1, respectively. Moreover, the anti-amyloid-β ability of crystalline and amorphous LG or LQ has been studied.