title: Cancer-relevant biochemical targets of cytotoxic Lonchocarpus flavonoids: a molecular docking analysis.
abstract: A molecular docking investigation has been carried out on cytotoxic prenylated flavonoids from Lonchocarpus haberi with cancer-relevant chemotherapeutic targets known to be inhibited by flavonoids. Two molecular docking programs, Molegro and ArgusDock, were used to compare the binding energies of Lonchocarpus flavonoids with other flavonoids, inhibitors, or known ligands, to aromatase (CYP 19), fatty acid synthase (FAS), xanthine oxidase (XO), cyclooxygenases (COX-1 and COX-2), lipoxygenase (LOX-3), ornithine decarboxylase (ODC), protein tyrosine kinase (PTK), phosphoinositide 3-kinase (PI3K), protein kinase C (PKC), topoisomerase II (ATP binding site), ATP binding cassette (ABC) transporter, and phospholipase A(2) (PLA). The Lonchocarpus flavonoids examined in this study exhibited docking energies comparable to or stronger than other flavonoids that had been previously shown to be effective inhibitors of these enzymes. Furthermore, prenylated flavonoids, such as the Lonchocarpus flavonoids and xanthohumol, generally showed greater binding energies than the non-prenylated flavonoids. We conclude, therefore, that the Lonchocarpus flavonoids possibly owe their cytotoxic activity by inhibition of one or more of these enzymes.
authors: Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA.
authors: Caitlin E
authors: CE
authors: Cassidy
authors: William N
authors: WN
authors: Setzer
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000493:pharmacokinetics; D003198:Computer Simulation; D029866:Derris / Q000737:chemistry*; D004791:Enzyme Inhibitors; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D010946:Plants, Medicinal; D011485:Protein Binding
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids