Molecular docking study of ethyl acetate fraction of Selaginella doederleinii Hieron extract as anti-Warburg effect in breast cancer

Abstract

Context: Aerobic glycolysis is a breast cancer hallmark that has become a novel target for anticancer therapy. GLUT1, HK2, PKM2, and LDHA are oncogenic proteins in the pathway. The compounds of ethyl acetate fraction of Selaginella doederleinii Hieron extract can be developed as aerobic glycolysis inhibitors by impeding the proteins’ activity. Aims: To analyze the anticancer activity of compounds of the ethyl acetate fraction of S. doederleinii via inhibiting oncogenic proteins in the aerobic glycolysis pathway. Methods: The 3D protein structures were obtained from the RCSB database. Ligands were compounds of the ethyl acetate fraction predicted to have a good oral bioavailability based on our previous study. The ligand structures were downloaded from the PubChem database. Docking and analysis of chemical interactions were performed using Autodock Vina in Pyrx and Discovery Studio 2020, respectively. Results: Some compounds interacted with the specific binding site of proteins with low binding affinity. Diosgenin interacted with GLUT1 and LDHA with the binding affinity of -11.8 and -9.6 kcal/mol. Frutinone A was found to bind PKM2 and LDHA with the binding affinity of -10.0 and -8.4 kcal/mol. Vitexin interacted with GLUT1 and PKM2 with the binding affinity of -10.4 and -10.0 kcal/mol. Valerodine and 5-hydroxyferulic acid methyl ester could bind HK2 with a binding affinity of -6.1 and -6.8 kcal/mol. Conclusions: The compounds of ethyl acetate fraction of S. doederleinii extract were predicted to inhibit GLUT1, HK2, PKM2, and LDHA. Therefore, these compounds could be developed as anti-breast cancer agents targeting the aerobic glycolysis pathway.