Bismuth(iii) β-thioxoketonates as antibiotics against Helicobacter pylori and as anti-leishmanial agents

Abstract

Nine different β-thioxoketones of general formula R¹C(O)CH₂C(S)R² (R¹ = C₆H₅, R² = C₆H₅L1; R¹ = C₆H₅, R² = p-CF₃C₆H₄L2; R¹ = p-MeOC₆H₄, R² = C₆H₅L3; R¹ = p-MeOC₆H₄, R² = p-CF₃C₆H₄L4; R¹ = C₅H₄N, R² = C₆H₅L5; R¹ = p-IC₆H₄, R² = C₆H₅L6; R¹ = C₆H₅, R² = p-IC₆H₄L7; R¹ = C₆H₅, R² = C₁₀H₇L8 and R¹ = CH₃, R² = C₆H₅L9) and their tris-substituted bismuth(III) complexes having the general formula [Bi{R¹C(O)CHC(S)R²}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.