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

Eight bismuth(III) complexes derived from the simple alpha-hydroxycarboxylic acids; gluconic (H-6-glu), tartaric (H-4-tar), mandelic (H-2-man), malic (H-3-mal) and glycolic (H-2-gly) have been synthesised and characterised. The complexes are formed through direct treatment of the organic acids with Bi(NO3)(3)center dot 5H(2)O ([Bi(H-2-tar)(H-3-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, [Bi-2(H-mal)(3)] 5, [Bi(gly)(H-gly)] 7), or through metathesis of the sodium salts with Bi(NO3)(3)center dot 5H(2)O ([Bi(H-3-glu)] 3). Reactions with both glucuronic and mucic acid proved to be unsuccessful. Small crystals of [Bi(gly)(4)(NO3)(4)(H2O)(4)]center dot 5H(2)O 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 +/- A 0.9 at 50.0 A mu M.