Bismuth(III) alpha-hydroxy carboxylates: highly selective toxicity of glycolates towards Leishmania major

Allan Loh, Yih Ching Ong, Victoria Louise Blair, Lukasz Kedzierski, Philip Craig Andrews

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10 Citations (Scopus)

Abstract

Eight bismuth(III) complexes derived from the simple α-hydroxycarboxylic acids; gluconic (H6-glu), tartaric (H4-tar), mandelic (H2-man), malic (H3-mal) and glycolic (H2-gly) have been synthesised and characterised. The complexes are formed through direct treatment of the organic acids with Bi(NO3)3·5H2O ([Bi(H2-tar)(H3-tar)] 2, [Bi(mal)(NO3)(H2O)2] 6, [Bi(gly)(NO3)(H2O)] 8) or Bi(O t Bu)3 ([Bi(H-tar)(H2O)2] 1, [Bi(man)(H-man)(H2O)] 4, [Bi2(H-mal)3] 5, [Bi(gly)(H-gly)] 7), or through metathesis of the sodium salts with Bi(NO3)3·5H2O ([Bi(H3-glu)] 3). Reactions with both glucuronic and mucic acid proved to be unsuccessful. Small crystals of [Bi(gly)4(NO3)4(H2O)4]·5H2O 8 were obtained from aqueous solution and analysed by synchrotron X-ray diffraction. The data were relatively poor but composition and connectivity were established, confirming and supporting other analyses. Those complexes which displayed sufficient solubility; 2, 4, 7 and 8, were tested for their anti-Leishmanial activity against parasite promastigotes and amastigotes, and for toxicity against human fibroblast cells. All four complexes and their parent acids showed no toxicity towards either the promastigotes or fibroblast cells. However, the two glycolate complexes showed selective toxicity towards amastigotes with complex 8 providing for a low % viability of 1.8 ± 0.9 at 50.0 µM.
Graphical Abstract
Novel bismuth(III) complexes derived from α-hydroxycarboxylic acids have been synthesised, characterised and assessed for their anti-leishmanial activity. The glycolate complexes are selectively toxic against parasite amastigotes, with all complexes being non-toxic towards promastigotes and human fibroblast cells
Original languageEnglish
Pages (from-to)1193-1203
Number of pages11
JournalJournal of Biological Inorganic Chemistry
Volume20
Issue number7
DOIs
Publication statusPublished - 2015

Keywords

  • Bismuth
  • α-Hydroxycarboxylic acid
  • Leishmania
  • Glycolate
  • Toxicity

Cite this

@article{47f3dee560b548ed998cc054ee6aaa2f,
title = "Bismuth(III) alpha-hydroxy carboxylates: highly selective toxicity of glycolates towards Leishmania major",
abstract = "Eight bismuth(III) complexes derived from the simple α-hydroxycarboxylic acids; gluconic (H6-glu), tartaric (H4-tar), mandelic (H2-man), malic (H3-mal) and glycolic (H2-gly) have been synthesised and characterised. The complexes are formed through direct treatment of the organic acids with Bi(NO3)3·5H2O ([Bi(H2-tar)(H3-tar)] 2, [Bi(mal)(NO3)(H2O)2] 6, [Bi(gly)(NO3)(H2O)] 8) or Bi(O t Bu)3 ([Bi(H-tar)(H2O)2] 1, [Bi(man)(H-man)(H2O)] 4, [Bi2(H-mal)3] 5, [Bi(gly)(H-gly)] 7), or through metathesis of the sodium salts with Bi(NO3)3·5H2O ([Bi(H3-glu)] 3). Reactions with both glucuronic and mucic acid proved to be unsuccessful. Small crystals of [Bi(gly)4(NO3)4(H2O)4]·5H2O 8 were obtained from aqueous solution and analysed by synchrotron X-ray diffraction. The data were relatively poor but composition and connectivity were established, confirming and supporting other analyses. Those complexes which displayed sufficient solubility; 2, 4, 7 and 8, were tested for their anti-Leishmanial activity against parasite promastigotes and amastigotes, and for toxicity against human fibroblast cells. All four complexes and their parent acids showed no toxicity towards either the promastigotes or fibroblast cells. However, the two glycolate complexes showed selective toxicity towards amastigotes with complex 8 providing for a low {\%} viability of 1.8 ± 0.9 at 50.0 µM.Graphical AbstractNovel bismuth(III) complexes derived from α-hydroxycarboxylic acids have been synthesised, characterised and assessed for their anti-leishmanial activity. The glycolate complexes are selectively toxic against parasite amastigotes, with all complexes being non-toxic towards promastigotes and human fibroblast cells",
keywords = "Bismuth, α-Hydroxycarboxylic acid, Leishmania, Glycolate, Toxicity",
author = "Allan Loh and Ong, {Yih Ching} and Blair, {Victoria Louise} and Lukasz Kedzierski and Andrews, {Philip Craig}",
year = "2015",
doi = "10.1007/s00775-015-1299-6",
language = "English",
volume = "20",
pages = "1193--1203",
journal = "Journal of Biological Inorganic Chemistry",
issn = "0949-8257",
publisher = "Springer-Verlag London Ltd.",
number = "7",

}

Bismuth(III) alpha-hydroxy carboxylates: highly selective toxicity of glycolates towards Leishmania major. / Loh, Allan; Ong, Yih Ching; Blair, Victoria Louise; Kedzierski, Lukasz; Andrews, Philip Craig.

In: Journal of Biological Inorganic Chemistry, Vol. 20, No. 7, 2015, p. 1193-1203.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Bismuth(III) alpha-hydroxy carboxylates: highly selective toxicity of glycolates towards Leishmania major

AU - Loh, Allan

AU - Ong, Yih Ching

AU - Blair, Victoria Louise

AU - Kedzierski, Lukasz

AU - Andrews, Philip Craig

PY - 2015

Y1 - 2015

N2 - Eight bismuth(III) complexes derived from the simple α-hydroxycarboxylic acids; gluconic (H6-glu), tartaric (H4-tar), mandelic (H2-man), malic (H3-mal) and glycolic (H2-gly) have been synthesised and characterised. The complexes are formed through direct treatment of the organic acids with Bi(NO3)3·5H2O ([Bi(H2-tar)(H3-tar)] 2, [Bi(mal)(NO3)(H2O)2] 6, [Bi(gly)(NO3)(H2O)] 8) or Bi(O t Bu)3 ([Bi(H-tar)(H2O)2] 1, [Bi(man)(H-man)(H2O)] 4, [Bi2(H-mal)3] 5, [Bi(gly)(H-gly)] 7), or through metathesis of the sodium salts with Bi(NO3)3·5H2O ([Bi(H3-glu)] 3). Reactions with both glucuronic and mucic acid proved to be unsuccessful. Small crystals of [Bi(gly)4(NO3)4(H2O)4]·5H2O 8 were obtained from aqueous solution and analysed by synchrotron X-ray diffraction. The data were relatively poor but composition and connectivity were established, confirming and supporting other analyses. Those complexes which displayed sufficient solubility; 2, 4, 7 and 8, were tested for their anti-Leishmanial activity against parasite promastigotes and amastigotes, and for toxicity against human fibroblast cells. All four complexes and their parent acids showed no toxicity towards either the promastigotes or fibroblast cells. However, the two glycolate complexes showed selective toxicity towards amastigotes with complex 8 providing for a low % viability of 1.8 ± 0.9 at 50.0 µM.Graphical AbstractNovel bismuth(III) complexes derived from α-hydroxycarboxylic acids have been synthesised, characterised and assessed for their anti-leishmanial activity. The glycolate complexes are selectively toxic against parasite amastigotes, with all complexes being non-toxic towards promastigotes and human fibroblast cells

AB - Eight bismuth(III) complexes derived from the simple α-hydroxycarboxylic acids; gluconic (H6-glu), tartaric (H4-tar), mandelic (H2-man), malic (H3-mal) and glycolic (H2-gly) have been synthesised and characterised. The complexes are formed through direct treatment of the organic acids with Bi(NO3)3·5H2O ([Bi(H2-tar)(H3-tar)] 2, [Bi(mal)(NO3)(H2O)2] 6, [Bi(gly)(NO3)(H2O)] 8) or Bi(O t Bu)3 ([Bi(H-tar)(H2O)2] 1, [Bi(man)(H-man)(H2O)] 4, [Bi2(H-mal)3] 5, [Bi(gly)(H-gly)] 7), or through metathesis of the sodium salts with Bi(NO3)3·5H2O ([Bi(H3-glu)] 3). Reactions with both glucuronic and mucic acid proved to be unsuccessful. Small crystals of [Bi(gly)4(NO3)4(H2O)4]·5H2O 8 were obtained from aqueous solution and analysed by synchrotron X-ray diffraction. The data were relatively poor but composition and connectivity were established, confirming and supporting other analyses. Those complexes which displayed sufficient solubility; 2, 4, 7 and 8, were tested for their anti-Leishmanial activity against parasite promastigotes and amastigotes, and for toxicity against human fibroblast cells. All four complexes and their parent acids showed no toxicity towards either the promastigotes or fibroblast cells. However, the two glycolate complexes showed selective toxicity towards amastigotes with complex 8 providing for a low % viability of 1.8 ± 0.9 at 50.0 µM.Graphical AbstractNovel bismuth(III) complexes derived from α-hydroxycarboxylic acids have been synthesised, characterised and assessed for their anti-leishmanial activity. The glycolate complexes are selectively toxic against parasite amastigotes, with all complexes being non-toxic towards promastigotes and human fibroblast cells

KW - Bismuth

KW - α-Hydroxycarboxylic acid

KW - Leishmania

KW - Glycolate

KW - Toxicity

UR - http://link.springer.com.ezproxy.lib.monash.edu.au/content/pdf/10.1007%2Fs00775-015-1299-6.pdf

U2 - 10.1007/s00775-015-1299-6

DO - 10.1007/s00775-015-1299-6

M3 - Article

VL - 20

SP - 1193

EP - 1203

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

SN - 0949-8257

IS - 7

ER -