title: Bismuth(III) β-thioxoketonates as antibiotics against Helicobacter pylori and as anti-leishmanial agents.
abstract: Nine different β-thioxoketones of general formula R(1)C(=O)CH2C(=S)R(2) (R(1) = C6H5, R(2) = C6H5L1; R(1) = C6H5, R(2) = p-CF3C6H4L2; R(1) = p-MeOC6H4, R(2) = C6H5L3; R(1) = p-MeOC6H4, R(2) = p-CF3C6H4L4; R(1) = C5H4N, R(2) = C6H5L5; R(1) = p-IC6H4, R(2) = C6H5L6; R(1) = C6H5, R(2) = p-IC6H4L7; R(1) = C6H5, R(2) = C10H7L8 and R(1) = CH3, R(2) = C6H5L9) and their tris-substituted bismuth(III) complexes having the general formula [Bi{R(1)C(=O)CHC(=S)R(2)}3] were synthesised and fully characterised. The solid state structure of [Bi{C5H4NC(=O)CHC(=S)C6H5}3] B5 was determined by crystallography and revealed that the three β-thioxoketonato ligands are bound to bismuth(III) centre in a bidentate fashion through O and S atoms. The bismuth(III) complexes and the corresponding thioxoketones were assessed for their activity against H. pylori. All of the bismuth(III) complexes were highly active against H. pylori having a MIC of greater than or equal to 3.125 μg mL(-1), while the free acids were essentially not toxic to the bacteria. The anti-leishmanial activity of all the bismuth(III) β-thioxoketonates and the corresponding free acids were assessed against L. major promastigotes. The toxicity towards human fibroblast cells was also assessed. All of the free β-thioxoketones were selectively toxic to the L. major promastigotes displaying some potential as anti-leishmanial agents. Among these [C6H5C(=O)CH2C(=S)C6H5] L1 and [C5H4NC(=O)CH2C(=S)C6H5] L5 showed comparable activity to that of Amphotericin B, killing about 80% of the L. major promastigotes at a concentration of 25 μM (6.0 μg mL(-1)). The bismuth(III) β-thioxoketonate complexes were toxic to both the L. major promastigotes and fibroblast cells at high concentrations, but gave no improvement in anti-leishmanial activity over the free β-thioxoketones.
authors.affiliation: School of Chemistry, Monash University, P.O. Box 23, Melbourne, Victoria 3800, Australia. phil.andrews@monash.edu.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Andrews
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Blair
authors.forename: Richard L
authors.initials: RL
authors.lastname: Ferrero
authors.forename: Peter C
authors.initials: PC
authors.lastname: Junk
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kedzierski
authors.forename: Roshani M
authors.initials: RM
authors.lastname: Peiris
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001729:Bismuth / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004952:Esters; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D007659:Ketones / Q000737:chemistry*; D007891:Leishmania / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D056831:Coordination Complexes; D004952:Esters; D007659:Ketones; D013438:Sulfhydryl Compounds; D001729:Bismuth