Screening of Indonesian Phytochemicals as Adenylate Kinase 2 Inhibitor for Cancer Therapy.

Abstract

Adenylate Kinase-2 (AK2) activity increases in cancer cells which results in high demand of energy supply through anaerobic metabolism. Bis(adenosine)-5’- pentaphosphate (Ap5a) is a synthetic compound that is able to inhibit AK family in cancer cells but it is still under development. There are 9,600 Indonesian phytochemicals which are predicted to have pharmacological activities and have been recorded in a database. Therefore this study aimed to identify Indonesian phytochemicals that can inhibit AK2 activity for cancer therapy. This was a bioinformatics study which used a molecular docking method. Because 3D structure of AK2 has not been established yet, MODELLER 9.19 program was used to create the AK2 model using AK1 template (PDB code: 1Z83). Ap5a, the standard compound, was obtained from zinc database (access code 96006032). Indonesian herbal plants which were registered in HerbalDB, had 3D structure in the PubChem database and met Lipinski’s criteria becameresearch samples. The binding energy of Ap5a/phytochemicals with AK2 was determined using the AutoDock Vina 1.5.6 program and the visualization of docking results was doneusing PyMol 1.7.4 program. BR-Xanthone A, Thwaitesixanthone, Chitranone, Sojagol, Withanolide D, Dehydrodeguelin, MLS001143540, (-)-sesamin, and strigol had the lowest docking score but only BR-Xanthone A (−11,30) and Thwaitesixanthone (−11,00) had lower binding energy than Ap5a. All nine phytochemicals bond to the binding sites of AK2. Similar conformation to Ap5a was observed in seven phytochemicals (BR-Xanthone A, Thwaitesixanthone, Chitranone, Withanolide D, MLS001143540, (-)-sesamin, and strigol). In conclusion, BR-Xanthone A is the most potential candidate for AK2 inhibitor in silico. This study proposes that BR-Xanthone A can have its anticancer property, as globally known, by inhibitingAK2.