title: Reverse screening approach to identify potential anti-cancer targets of dipyridamole.
abstract: Dipyridamole (DIP) inhibits thrombus formation when given chronically, and causes vasodilation over a short time. To date, DIP can increase the anticancer drugs (5-fluorouracil, methotrexate, piperidine, vincristine) concentration in cancer cells and hence enhance the efficacy of treatment cancer. The inhibition of DIP may result in increased 5-fluorouracil efficacy and diminish the drug side effects. But the actual molecular targets remain unknown. In this study, reverse protein-ligands docking, and quantum mechanics were used to search for the potential molecular targets of DIP. The quantum mechanics calculation was performed by using Gaussian 03 program package. Reverse pharmacophore mapping was used to search for potential molecular target candidates for a given small molecule. The docking study was used for exploring the potential anti-cancer targets of dipyridamole. The two predicted binders with the statistically significant prediction are dihydropyrimidine dehydrogenase (DPD) (PDB Id: 1GTE) and human spindle checkpoint kinase Bub1 (PDB Id: 3E7E). Structure analysis suggests that electrostatic interaction and hydrogen bonding play an important role in their binding process. The strong functional linkage of DIP and 5FU supports our prediction. In conclusion, these results generate a tractable set of anticancer proteins. The exploration of polypharmacology will provide us new opportunities in treating systematic diseases, such as the cancers. The results would generate a tractable set of anticancer target proteins for future experimental validations.
authors.affiliation: School of Life Science and Technology, Changchun University of Science and Technology Changchun 130022, China.
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Ge
authors.affiliation: College of Food Science and Engineering, Jilin Agricultural University Changchun 130118, China.
authors.forename: Dong-Ling
authors.initials: DL
authors.lastname: Zhan
authors.affiliation: School of Life Science and Technology, Changchun University of Science and Technology Changchun 130022, China.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Changchun University of Science and Technology Changchun 130022, China.
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Song
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University Changchun 130023, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Han
keywords: Dipyridamole; anticancer target proteins; reverse protein-ligand docking