Therapeutic properties of isoliquiritigenin with molecular modeling studies: investigation of anti-pancreatic acinar cell tumor and HMG-CoA reductase inhibitor activity for treatment of hypercholesterolemia

Abstract

Introduction: Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have anti-tumor activity in vitro and in vivo. HMG-CoA reductase inhibitors, called statins, are used to reduce the risk of heart disease by lowering blood cholesterol levels.

Material and methods: HMG-CoA reductase activity was determined according to the method described by Takahashi et al. The structure of human HMG-COA reductase in the resolution of 2.22 Å with the X-ray diffraction method (PDB ID: 1HWK) was obtained from the PDB database.

Results: In our study, the inhibitory activity of isoliquiritigenin towards HMG-CoA reductase showed a lower value of IC₅₀ = 193.77 ±14.85 μg/ml. For a better understanding of biological activities and interactions, the molecular docking study was performed. The results of molecular docking revealed that isoliquiritigenin with a docking score of -6.740 has a strong binding affinity to HMG-COA reductase. Therefore, this compound could be considered as a potential inhibitor for the enzyme. Also, the activity of isoliquiritigenin against common human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47, was evaluated.

Conclusions: The cells treated with isoliquiritigenin were assessed by MTT assay for 48 h as regards the cytotoxicity and anti-human pancreatic acinar cell tumor properties in normal (HUVEC) and human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47. The IC₅₀ values of isoliquiritigenin were 262, 389, and 211 μg/ml against 266-6, TGP49, and TGP47 cell lines, respectively. The viability of the human pancreatic acinar cell tumor cell line decreased dose-dependently in the presence of isoliquiritigenin. After clinical study, isoliquiritigenin can be utilized as an efficient drug in the treatment of human pancreatic acinar cell tumor in humans.

Keywords: HMG-COA reductase; human pancreatic acinar cell tumor; isoliquiritigenin; molecular docking.

Figure 1

Anti-pancreatic acinar cell tumor effects of isoliquiritigenin (concentrations of 0–1000 μg/ml) against 266-6 cell line

Figure 2

Anti-pancreatic acinar cell tumor effects of isoliquiritigenin (concentrations of 0–1000 μg/ml) against TGP49 cell line.

Figure 3

Anti-pancreatic acinar cell tumor effects of isoliquiritigenin (concentrations of 0–1000 μg/ml) against TGP47 cell line

Figure 4

Cytotoxicity activities of isoliquiritigenin against normal (HUVEC) cell line

Figure 5

The docking pose of isoliquiritigenin among HMG-COA reductase

Figure 6

Interactions of isoliquiritigenin and HMG-COA reductase. Green dashed lines indicate hydrogen bonds, and semicircles show hydrophobic contacts

Figure 7

The first active site in the HMG-COA reductase structure