Appended 1,2-naphthoquinones as Anticancer Agents 1: Synthesis, Structural, Spectral and Antitumor Activities of Ortho-naphthaquinone Thiosemicarbazone and its Transition Metal Complexes

Abstract

Copper(II), nickel(II), palladium(II) and platinum(II) complexes of ortho-naphthaquinone thiosemicarbazone were synthesized and characterized by spectroscopic studies. In both solution (NMR) and solid state (IR, single-crystal X-ray diffraction determination) the free ligand NQTS exists as the thione form. The Pd complex (X-ray) crystallizes as the H-bonded dimer, [Pd(NQTS)Cl]2·2DMSO, where palladium(II) coordinates in a square planar configuration to the monodeprotonated, tridentate thiosemicarbazone ligand. The nickel(II) complex shows 1:2 metal to ligand stoichiometry while the other complexes exhibit 1:1 metal-ligand compositions. In vitro anticancer studies on MCF7 human breast cancer cells reveal that adding a thiosemicarbazone pharmacophore to the parent quinone carbonyl considerably enhances its antiproliferative activity. Among the metal complexes, the nickel compound exhibits the lowest IC50 value (2.25 µM) suggesting a different mechanism of action involving inhibition of topoisomerase II activity.

Department(s)

Chemistry

Keywords and Phrases

1,2 naphthoquinone; 2 naphthaquinone thiosemicarbazone; antineoplastic agent; copper complex; DNA topoisomerase; naphthol derivative; nickel complex; palladium complex; platinum complex; thiosemicarbazone derivative; transition element; unclassified drug; cancer cell; cell strain; controlled study; drug conformation; drug synthesis; enzyme activity; human; human cell; hydrogen bond; IC 50; infrared spectroscopy; metal binding; metastasis inhibition; nuclear magnetic resonance; pharmacophore; proteinase inhibition; solid state; stoichiometry; X ray crystallography; X ray powder diffraction; metal complexes

International Standard Serial Number (ISSN)

0020-1693

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2004 Elsevier, All rights reserved.

Publication Date

01 Jan 2004

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