title: Impact of metal ions on netilmicin-melanin interaction.
abstract: Netilmicin, which is mainly used as the sulfate, is a semisynthetic, water soluble aminoglycoside antibiotic obtained by chemical modification of sisomicin. It is active against both Gram-positive and Gram-negative bacteria, including strains which are resistant to other aminoglycosides. Netilmicin form complexes with melanin. The aim of the presented work was to examine the effect of Cu2+, Zn2+, Ca2+ and Mg2+ on netilmicin binding to synthetic DOPA-melanin. It has been demonstrated that metal ions decrease the amount of antibiotic bound to melanin as compared with netilmicin-melanin complexes obtained in the absence of metals. It has been also shown that only one class of binding sites participates in netilmicin-[melanin-metal ion] complexes formation with the association constant K approximately 10(3) M(-1). The obtained results demonstrate that Cu2+, Zn2+, Ca2+ and Mg2+ ions modify the interaction between netilmicin and melanin biopolymer. The blocking of some active centers in melanin molecules by metal ions, which potentially exist in living systems, may influence the clinical therapeutic efficiency as well as the undesirable side effects of netilmicin.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, Jagiellońska 4, PL-41-200 Sosnowiec, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Wrześniok
authors.forename: Ewa
authors.initials: E
authors.lastname: Buszman
authors.forename: Magdalena
authors.initials: M
authors.lastname: Grzegorczyk
authors.forename: Aneta
authors.initials: A
authors.lastname: Grzegorczyk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Hryniewicz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002413:Cations, Divalent; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000737:chemistry* / Q000378:metabolism; D009428:Netilmicin / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002413:Cations, Divalent; D009428:Netilmicin; D004295:Dihydroxyphenylalanine; C040616:DOPA melanin; D003300:Copper; D008274:Magnesium; D015032:Zinc; D002118:Calcium