In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 4; p. 417
• Main Authors: Malami, Ibrahim, Abdul, Ahmad Bustamam, Abdullah, Rasedee, Bt Kassim, Nur Kartinee, Waziri, Peter, Christopher Etti, Imaobong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08-04-2016; MDPI
• Subjects: Adenosine Diphosphate - biosynthesis; alpinetin; Alpinia - enzymology; Alpinia mutica; amino acid active site residues; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Cancer therapies; Cell growth; Cell Proliferation - drug effects; Chemotherapy; Clinical trials; Computer Simulation; Cytotoxicity; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - therapeutic use; Enzymes; Flavanones - chemistry; Flavanones - therapeutic use; flavokawain B; Flavonoids - chemistry; Flavonoids - therapeutic use; Humans; in silico; Kinases; Ligands; Medical research; Metabolism; Molecular Docking Simulation; Natural products; Neoplasms - drug therapy; Neutropenia; nucleoside analogues; Phosphorylation; Rhizome - enzymology; UCK2; Uridine Kinase - antagonists & inhibitors; Uridine Kinase - chemistry; Selangor Malaysia; Malaysia; UCK2; Alpinia mutica; amino acid active site residues; nucleoside analogues; in silico; flavokawain B; alpinetin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21040417

Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective UCK2 inhibitors of natural origin using bioinformatics tools. An in vitro kinase assay was established by measuring the amount of ADP production in the presence of ATP and 5-fluorouridine as a substrate. Molecular docking studies revealed an interesting ligand interaction with the UCK2 protein for both flavokawain B and alpinetin. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity in vitro. In conclusion, we have identified flavokawain B and alpinetin as potential natural UCK2 inhibitors as determined by their interactions with UCK2 protein using in silico molecular docking studies. This can provide information to identify lead candidates for further drug design and development.