Objectives: This study aimed to predict the binding pose of bufadienolides from Kalanchoe pinnata on Na+/K+-ATPase using molecular docking in comparison with a known inhibitor, and to determine the important functional group of bufadienolide that is responsible for good binding. Material and methods: Docking was performed on the receptor file (PDB ID: 4RES) using AutoDock 4.2. Before docking, the complex structure of ligand-receptor was minimized using AMBER 14. The physico-chemical properties were predicted using Biovia Draw. Results: The sterical hindrance of Glu117 to the 1,3,5-orthoacetate moiety was removed after minimisation. The docking energy, Polar Surface Area (PSA) and A Log P showed good correlation with the experimental data. The 14-OH of all bufadienolides formed a hydrogen bond with Thr797. However, the energy breakdown analysis of docking result demonstrated that C1 has the highest ligand efficiency with the strongest hydrogen bond and electrostatic energies, followed by C2 and C3. The hydrogen bond from the 10-OH and the orthoacetate ring in C1 was stronger than that of 10-CH2OH in C2 and 10-OH in C3. Conclusion: The best activity of C1, as compared to C2 and C3, was due to the presence of 1,3,5-orthoacetate moiety, 10-CHO, 11-OH, and 14-OH. In addition, the 11-OH group appeared to decrease the toxicity of the bufadienolide by improving its selectivity to the receptor. This result is expected to be useful in the further development of bufadienolide-based inhibitor for anticancer.
Key words: Bufadienolide, Kalanchoe Pinnata, Anticancer, Na+/K+-Atpase, Molecular Docking.