title: In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica.
abstract: 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.
authors.affiliation: MAKNA-Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. keepibinformed@yahoo.co.uk.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Malami
authors.affiliation: MAKNA-Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. zer2crystals@gmail.com.
authors.forename: Ahmad Bustamam
authors.initials: AB
authors.lastname: Abdul
authors.affiliation: Department of Veterinary Pathology and Microbiology, Faculty of Veterinary, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. rasedee@gmail.com.
authors.forename: Rasedee
authors.initials: R
authors.lastname: Abdullah
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. kartinee@upm.edu.my.
authors.forename: Nur Kartinee
authors.initials: NK
authors.lastname: Bt Kassim
authors.affiliation: MAKNA-Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. petermwaziri@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Waziri
authors.affiliation: Department of Pharmacology and Toxicology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. ettimaobong@gmail.com.
authors.forename: Imaobong
authors.initials: I
authors.lastname: Christopher Etti
mesh_terms: D000244:Adenosine Diphosphate / Q000096:biosynthesis; D032429:Alpinia / Q000201:enzymology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D044950:Flavanones / Q000737:chemistry* / Q000627:therapeutic use; D005419:Flavonoids / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy; D027343:Rhizome / Q000201:enzymology; D014541:Uridine Kinase / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D008024:Ligands; C436748:alpinetin; C452039:flavokawain B; D000244:Adenosine Diphosphate; D014541:Uridine Kinase
keywords: Alpinia mutica; UCK2; alpinetin; amino acid active site residues; flavokawain B; in silico; nucleoside analogues