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001-es BibID:	BIBFORM118663
035-os BibID:	(Scopus)85184295538 (WOS)001158211000001
Első szerző:	Pósa Vivien
Cím:	A Comparative Study on the Complexation of the Anticancer Iron Chelator VLX600 with Essential Metal Ions / Pósa, Vivien; Federa, Anja; Cseh, Klaudia; Wenisch, Dominik; Spengler, Gabriella; May, Nóra V.; Lihi, Norbert; Samu, Gergely F.; Jakupec, Michael A.; Keppler, Bernhard K.; Kowol, Christian R.; Enyedy, Éva A.
Dátum:	2024
ISSN:	0020-1669 1520-510X
Megjegyzések:	As cancer cells exhibit an increased uptake of iron, targeting the interaction with iron has become a straightforward strategy in the fight against cancer. This work comprehensively characterizes the chemical properties of 6-methyl-3-{(2E)-2-[1-(2-pyridinyl)-ethylidene]-hydrazino}-5H-[1,2,4]-triazino-[5,6-b]-indole (VLX600), a clinically investigated iron chelator, in solution. Its protonation processes, lipophilicity, and membrane permeability as well as its complexation with essential metal ions were investigated using UV-visible, electron paramagnetic resonance, and NMR spectroscopic and computational methods. Formation constants revealed the following order of metal binding affinity at pH 7.4: Cu-(II) > Fe-(II) > Zn-(II). The structures of VLX600 (denoted as HL) and the coordination modes in its metal complexes [Cu-(II)-(LH)-Cl-2], [Cu-(II)-(L)-(CH3OH)-Cl], [Zn-(II)-(LH)-Cl-2], and [Fe-(II)-(LH)(2)]-(NO3)(2) were elucidated by single-crystal X-ray diffraction. Redox properties of the iron complexes characterized by cyclic voltammetry showed strong preference of VLX600 toward Fe-(II) over Fe-(III). In vitro cytotoxicity of VLX600 was determined in six different human cancer cell lines, with IC50 values ranging from 0.039 to 0.51 mu M. Premixing VLX600 with Fe-(III), Zn-(II), and Cu-(II) salts in stoichiometric ratios had a rather little effect overall, thus neither potentiating nor abolishing cytotoxicity. Together, although clinically investigated as an iron chelator, this is the first comprehensive solution study of VLX600 and its interaction with physiologically essential metal ions.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Coordination Complexes Copper Ferric Compounds Ferrous Compounds Humans Hydrazones Ions Iron Iron Chelating Agents Metals Triazoles
Megjelenés:	Inorganic Chemistry. - 63 : 5 (2024), p. 2401-2417. -
További szerzők:	Federa, Anja Cseh Klaudia Wenisch, Dominik Spengler, Gabriella May Nóra Veronika Lihi Norbert (1990-) (vegyész) Samu Gergely Ferenc Jakupec, Michael A. Keppler, Bernhard K. Kowol, Christian R. Enyedy Éva Anna (1975-) (vegyész)
Pályázati támogatás:	NKFIH TKP-2021-EGA-32 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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