title: Bismuth(III) α-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(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 nontoxic towards promastigotes and human fibroblast cells.
authors.affiliation: School of Chemistry, Monash University, Clayton, Melbourne, VIC, 3800, Australia.
authors.forename: Allan
authors.initials: A
authors.lastname: Loh
authors.affiliation: School of Chemistry, Monash University, Clayton, Melbourne, VIC, 3800, Australia.
authors.forename: Yih Ching
authors.initials: YC
authors.lastname: Ong
authors.affiliation: School of Chemistry, Monash University, Clayton, Melbourne, VIC, 3800, Australia.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Blair
authors.affiliation: Walter and Eliza Institute of Medical Research, Parkville, Melbourne, VIC, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Melbourne, 3010, Australia.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kedzierski
authors.affiliation: School of Chemistry, Monash University, Clayton, Melbourne, VIC, 3800, Australia. phil.andrews@monash.edu.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Andrews
mesh_terms: D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology; D001729:Bismuth / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology*; D056831:Coordination Complexes / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects / Q000469:parasitology; D006016:Glycolates / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D018320:Leishmania major / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D000977:Antiparasitic Agents; D002264:Carboxylic Acids; D056831:Coordination Complexes; D006016:Glycolates; C031149:glycolic acid; D001729:Bismuth
keywords: Bismuth; Glycolate; Leishmania; Toxicity; α-Hydroxycarboxylic acid