title: Metal coordination and tyrosinase inhibition studies with Kojic-βAla-Kojic.
abstract: Kojic acid is a natural antifungal and antibacterial agent that has been extensively studied for its tyrosinase inhibitory and metal coordination properties. Tyrosinase is a metalloenzyme with two copper ions in the active site. It is widely accepted that the tyrosinase inhibitory activity of kojic acid is related to its ability to coordinate metals. Over the past five years, we have used kojic acid to synthesize new and efficient bis-kojic acid chelators of iron and aluminium. In parallel, we investigated whether the de novo designed ligands could interfere with proper tyrosinase functioning. The present study combines our experience with inhibition and coordination studies of the new ligand: Kojic-βAla-Kojic. Research aimed at the assembly of a new potent tyrosinase inhibitor was based on the well-known crystal structure of the enzyme. Two questions were whether two kojic acids could act better than one and to what extent the length and kind of linker could ameliorate metal coordination, and inhibitory activity. Our results show that Kojic-βAla-Kojic has high affinity for Fe(III), Al(III), Zn(II), and Cu(II) and strong tyrosinase inhibitory effect and it can be proposed for use in industrial and pharmaceutical applications.
authors.affiliation: Department of Chemical and Geological Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari 09042, Italy. Electronic address: lachowicz@unica.it.
authors.forename: Joanna Izabela
authors.initials: JI
authors.lastname: Lachowicz
authors.affiliation: Department of Chemical and Geological Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari 09042, Italy.
authors.forename: Valeria Marina
authors.initials: VM
authors.lastname: Nurchi
authors.affiliation: Department of Chemical and Geological Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari 09042, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Crisponi
authors.affiliation: Department of Chemical and Geological Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari 09042, Italy.
authors.forename: Maria de Guadalupe Jaraquemada
authors.initials: Mde G
authors.lastname: Pelaez
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari 09042, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rescigno
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, Wroclaw 50-383, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Stefanowicz
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, Wroclaw 50-383, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Cal
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, Wroclaw 50-383, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Szewczuk
mesh_terms: D000535:Aluminum / Q000737:chemistry; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D004355:Drug Stability; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D011753:Pyrones / Q000737:chemistry* / Q000494:pharmacology*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C000611295:(5-hydroxy-4-oxo-4H-pyran-2-yl)methyl 3-((((5-hydroxy-4-oxo-4H-pyran-2 yl)methoxy)carbonyl)amino)propanoate; D056831:Coordination Complexes; D004791:Enzyme Inhibitors; D011753:Pyrones; D015091:beta-Alanine; C011890:kojic acid; D000535:Aluminum; D007501:Iron; D014442:Monophenol Monooxygenase
keywords: Kojic acid; Metal complexes; Synthesis; Tyrosinase inhibitor