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

Loh, A; Ong, YC; Blair, VL; Kedzierski, L; Andrews, PC

Author(s): Loh, A; Ong, YC; Blair, VL; Kedzierski, L; Andrews, PC;
Details: Publication Year 2015-09-28,Volume 20,Issue #7,Page 1193-203
Journal Title: J Biol Inorg Chem
Publication Type: Journal Article
Abstract: Eight bismuth(III) complexes derived from the simple alpha-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 microM. Novel bismuth(III) complexes derived from alpha-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.
Publisher: Springer
Research Division(s): Inflammation
PubMed ID: 26411702
Publisher's Version: https://doi.org/10.1007/s00775-015-1299-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2015-10-23 03:05:36

Last Modified: 2015-10-23 03:10:52