Comparative stability, cytotoxicity and anti-leishmanial activity of analogous organometallic Sb(V) and Bi(V) acetato complexes

Sb confirms potential while Bi fails the test

Rebekah N. Duffin, Victoria L. Blair, Lukasz Kedzierski, Philip C. Andrews

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A series of sixteen triphenyl Bi(V) and Sb(V) acetato complexes of general formula [MPh3(O2CCR)2] and one oxido-bridge antimony complex [(SbPh3(O2C–O–C([dbnd]O)Me))2O], have been synthesised and characterised, thirteen of which are novel. The solid-state structures of fifteen of the complexes have been successfully authenticated by single crystal X-ray diffraction. All structures, excluding the oxido-bridge antimony complex, adopt a typical trigonal bipyramidal confirmation with the phenyl rings in a propeller-like orientation in the equatorial plane. Fourteen of the complexes were screened for their anti-leishmanial activity and cytotoxicity towards mammalian cells. The Bi(V) complexes were found to be unstable in DMEM culture media and to be severely toxic towards mammalian cells, with IC50 values in the range 11.4 μM–19.8 μM. In contrast, the Sb(V) complexes demonstrated a high degree of stability and selectivity, with IC50 values 6.18–19.1 μM for the promastigote assay, and of 73.8–≤100 μM for the human fibroblasts. Assessment of the Sb(V) complexes against the clinically relevant amastigote form of these parasites at 10 μM showed all but the oxido-bridged complex to be effective, with % infection values ranging from 7.0 ± 1.7–40.5 ± 2.0.

Original languageEnglish
Pages (from-to)151-162
Number of pages12
JournalJournal of Inorganic Biochemistry
Volume189
DOIs
Publication statusPublished - 1 Dec 2018

Cite this

@article{3aecde13949d4adcbc5f960d10e87716,
title = "Comparative stability, cytotoxicity and anti-leishmanial activity of analogous organometallic Sb(V) and Bi(V) acetato complexes: Sb confirms potential while Bi fails the test",
abstract = "A series of sixteen triphenyl Bi(V) and Sb(V) acetato complexes of general formula [MPh3(O2CCR)2] and one oxido-bridge antimony complex [(SbPh3(O2C–O–C([dbnd]O)Me))2O], have been synthesised and characterised, thirteen of which are novel. The solid-state structures of fifteen of the complexes have been successfully authenticated by single crystal X-ray diffraction. All structures, excluding the oxido-bridge antimony complex, adopt a typical trigonal bipyramidal confirmation with the phenyl rings in a propeller-like orientation in the equatorial plane. Fourteen of the complexes were screened for their anti-leishmanial activity and cytotoxicity towards mammalian cells. The Bi(V) complexes were found to be unstable in DMEM culture media and to be severely toxic towards mammalian cells, with IC50 values in the range 11.4 μM–19.8 μM. In contrast, the Sb(V) complexes demonstrated a high degree of stability and selectivity, with IC50 values 6.18–19.1 μM for the promastigote assay, and of 73.8–≤100 μM for the human fibroblasts. Assessment of the Sb(V) complexes against the clinically relevant amastigote form of these parasites at 10 μM showed all but the oxido-bridged complex to be effective, with {\%} infection values ranging from 7.0 ± 1.7–40.5 ± 2.0.",
author = "Duffin, {Rebekah N.} and Blair, {Victoria L.} and Lukasz Kedzierski and Andrews, {Philip C.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/j.jinorgbio.2018.08.015",
language = "English",
volume = "189",
pages = "151--162",
journal = "Journal of Inorganic Biochemistry",
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TY - JOUR

T1 - Comparative stability, cytotoxicity and anti-leishmanial activity of analogous organometallic Sb(V) and Bi(V) acetato complexes

T2 - Sb confirms potential while Bi fails the test

AU - Duffin, Rebekah N.

AU - Blair, Victoria L.

AU - Kedzierski, Lukasz

AU - Andrews, Philip C.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - A series of sixteen triphenyl Bi(V) and Sb(V) acetato complexes of general formula [MPh3(O2CCR)2] and one oxido-bridge antimony complex [(SbPh3(O2C–O–C([dbnd]O)Me))2O], have been synthesised and characterised, thirteen of which are novel. The solid-state structures of fifteen of the complexes have been successfully authenticated by single crystal X-ray diffraction. All structures, excluding the oxido-bridge antimony complex, adopt a typical trigonal bipyramidal confirmation with the phenyl rings in a propeller-like orientation in the equatorial plane. Fourteen of the complexes were screened for their anti-leishmanial activity and cytotoxicity towards mammalian cells. The Bi(V) complexes were found to be unstable in DMEM culture media and to be severely toxic towards mammalian cells, with IC50 values in the range 11.4 μM–19.8 μM. In contrast, the Sb(V) complexes demonstrated a high degree of stability and selectivity, with IC50 values 6.18–19.1 μM for the promastigote assay, and of 73.8–≤100 μM for the human fibroblasts. Assessment of the Sb(V) complexes against the clinically relevant amastigote form of these parasites at 10 μM showed all but the oxido-bridged complex to be effective, with % infection values ranging from 7.0 ± 1.7–40.5 ± 2.0.

AB - A series of sixteen triphenyl Bi(V) and Sb(V) acetato complexes of general formula [MPh3(O2CCR)2] and one oxido-bridge antimony complex [(SbPh3(O2C–O–C([dbnd]O)Me))2O], have been synthesised and characterised, thirteen of which are novel. The solid-state structures of fifteen of the complexes have been successfully authenticated by single crystal X-ray diffraction. All structures, excluding the oxido-bridge antimony complex, adopt a typical trigonal bipyramidal confirmation with the phenyl rings in a propeller-like orientation in the equatorial plane. Fourteen of the complexes were screened for their anti-leishmanial activity and cytotoxicity towards mammalian cells. The Bi(V) complexes were found to be unstable in DMEM culture media and to be severely toxic towards mammalian cells, with IC50 values in the range 11.4 μM–19.8 μM. In contrast, the Sb(V) complexes demonstrated a high degree of stability and selectivity, with IC50 values 6.18–19.1 μM for the promastigote assay, and of 73.8–≤100 μM for the human fibroblasts. Assessment of the Sb(V) complexes against the clinically relevant amastigote form of these parasites at 10 μM showed all but the oxido-bridged complex to be effective, with % infection values ranging from 7.0 ± 1.7–40.5 ± 2.0.

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