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

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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(OtBu)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.

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Authors and Affiliations

  1. School of Chemistry, Monash University, Clayton, Melbourne, VIC, 3800, Australia

    Allan Loh, Yih Ching Ong, Victoria L. Blair & Philip C. Andrews

  2. Walter and Eliza Institute of Medical Research, Parkville, Melbourne, VIC, 3052, Australia

    Lukasz Kedzierski

  3. Department of Medical Biology, University of Melbourne, Parkville, Melbourne, 3010, Australia

    Lukasz Kedzierski

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  1. Allan Loh
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  2. Yih Ching Ong
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  3. Victoria L. Blair
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  4. Lukasz Kedzierski
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  5. Philip C. Andrews
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Correspondence to Philip C. Andrews.

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Loh, A., Ong, Y.C., Blair, V.L. et al. Bismuth(III) α-hydroxy carboxylates: highly selective toxicity of glycolates towards Leishmania major . J Biol Inorg Chem 20, 1193–1203 (2015). https://doi.org/10.1007/s00775-015-1299-6

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