Title

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

Library of Congress Subject Headings

Antineoplastic agents
Metal complexes

International Standard Serial Number (ISSN)

00201693

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2004 Elsevier, All rights reserved.


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