Cytotoxic activity of expanded coordination bis-thiosemicarbazones and copper complexes thereof

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Abstract

A series of bis-thiosemicarbazone agents with coordinating groups capable of multiple metal coordination modes has been generated and evaluated for potential cytotoxic effects against melanoma (MelRm) and breast adenocarcinoma (MCF-7) cell lines. The bis-thiosemicarbazones in this study generally demonstrated superior cytotoxic activity against MelRm than MCF-7 in the absence of metal ion supplementation, but in most cases could not be considered superior to the reference thiosemicarbazone Dp44mT. The key structural features for the cytotoxic activity were the central metal binding atom on the aromatic core, the thiocarbonyl residue and the nature of substitution on the N4-terminus in terms of size and lipophilicity. The cytotoxicity of bis-thiosemicarbazone ligands improved significantly with Cu(II) supplementation, particularly against MCF-7 cells. The mechanism of cytotoxicity of bis-thiosemicarbazones was proposed to be dependent on the combined effect of metal mobilisation and ROS generation which is so called a 'double-punch effect'.
Original languageEnglish
Pages (from-to)931-944
Number of pages14
JournalJournal of Biological Inorganic Chemistry
Volume21
Issue number8
DOIs
Publication statusPublished - 2016

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Thiosemicarbazones
Metals
MCF-7 Cells
Cytotoxicity
Metal ions
Melanoma
Adenocarcinoma
Breast
Substitution reactions
Cells
copper-thiosemicarbazone complex
Ions
Ligands
Cell Line
Atoms

Cite this

@article{bf033062cfd14bbb8e4d9d1b8e85c6fe,
title = "Cytotoxic activity of expanded coordination bis-thiosemicarbazones and copper complexes thereof",
abstract = "A series of bis-thiosemicarbazone agents with coordinating groups capable of multiple metal coordination modes has been generated and evaluated for potential cytotoxic effects against melanoma (MelRm) and breast adenocarcinoma (MCF-7) cell lines. The bis-thiosemicarbazones in this study generally demonstrated superior cytotoxic activity against MelRm than MCF-7 in the absence of metal ion supplementation, but in most cases could not be considered superior to the reference thiosemicarbazone Dp44mT. The key structural features for the cytotoxic activity were the central metal binding atom on the aromatic core, the thiocarbonyl residue and the nature of substitution on the N4-terminus in terms of size and lipophilicity. The cytotoxicity of bis-thiosemicarbazone ligands improved significantly with Cu(II) supplementation, particularly against MCF-7 cells. The mechanism of cytotoxicity of bis-thiosemicarbazones was proposed to be dependent on the combined effect of metal mobilisation and ROS generation which is so called a 'double-punch effect'.",
keywords = "Bis-thiosemicarbazone (Bis-TSC), Copper, Cytotoxicity, Reactive oxygen species (ROS)",
author = "Fady Akladios and Scott Andrew and Christopher Parkinson",
note = "Includes bibliographical references.",
year = "2016",
doi = "10.1007/s00775-016-1390-7",
language = "English",
volume = "21",
pages = "931--944",
journal = "Journal of Biological Inorganic Chemistry",
issn = "0949-8257",
publisher = "Springer-Verlag London Ltd.",
number = "8",

}

TY - JOUR

T1 - Cytotoxic activity of expanded coordination bis-thiosemicarbazones and copper complexes thereof

AU - Akladios, Fady

AU - Andrew, Scott

AU - Parkinson, Christopher

N1 - Includes bibliographical references.

PY - 2016

Y1 - 2016

N2 - A series of bis-thiosemicarbazone agents with coordinating groups capable of multiple metal coordination modes has been generated and evaluated for potential cytotoxic effects against melanoma (MelRm) and breast adenocarcinoma (MCF-7) cell lines. The bis-thiosemicarbazones in this study generally demonstrated superior cytotoxic activity against MelRm than MCF-7 in the absence of metal ion supplementation, but in most cases could not be considered superior to the reference thiosemicarbazone Dp44mT. The key structural features for the cytotoxic activity were the central metal binding atom on the aromatic core, the thiocarbonyl residue and the nature of substitution on the N4-terminus in terms of size and lipophilicity. The cytotoxicity of bis-thiosemicarbazone ligands improved significantly with Cu(II) supplementation, particularly against MCF-7 cells. The mechanism of cytotoxicity of bis-thiosemicarbazones was proposed to be dependent on the combined effect of metal mobilisation and ROS generation which is so called a 'double-punch effect'.

AB - A series of bis-thiosemicarbazone agents with coordinating groups capable of multiple metal coordination modes has been generated and evaluated for potential cytotoxic effects against melanoma (MelRm) and breast adenocarcinoma (MCF-7) cell lines. The bis-thiosemicarbazones in this study generally demonstrated superior cytotoxic activity against MelRm than MCF-7 in the absence of metal ion supplementation, but in most cases could not be considered superior to the reference thiosemicarbazone Dp44mT. The key structural features for the cytotoxic activity were the central metal binding atom on the aromatic core, the thiocarbonyl residue and the nature of substitution on the N4-terminus in terms of size and lipophilicity. The cytotoxicity of bis-thiosemicarbazone ligands improved significantly with Cu(II) supplementation, particularly against MCF-7 cells. The mechanism of cytotoxicity of bis-thiosemicarbazones was proposed to be dependent on the combined effect of metal mobilisation and ROS generation which is so called a 'double-punch effect'.

KW - Bis-thiosemicarbazone (Bis-TSC)

KW - Copper

KW - Cytotoxicity

KW - Reactive oxygen species (ROS)

U2 - 10.1007/s00775-016-1390-7

DO - 10.1007/s00775-016-1390-7

M3 - Article

C2 - 27645502

VL - 21

SP - 931

EP - 944

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

SN - 0949-8257

IS - 8

ER -