title: Anti-Leishmanial activity of homo- and heteroleptic bismuth(III) carboxylates.
abstract: Bismuth(III) complexes of NSAIDs (Non-Steroidal Anti Inflammatory Drugs) and substituted benzoic acids (o-methoxybenzoic acid, m-methoxybenzoic acid, o-nitrobenzoic acid, 3,5-diacetamidobenzoic acid, and 5-[(R/S)-2,3-dihydroxypropyl carbamoyl]-2-pyridine carboxylic acid) have been synthesised and fully characterised. Two new bis-carboxylato bismuth complexes have been characterised by single crystal X-ray diffraction, namely [PhBi(o-MeOC(6)H(4)CO(2))(2)(bipy)]·0.5EtOH (bipy=2,2'-bipyridine) and [PhBi(C(9)H(11)N(2)O(3)CO(2))(2)(H(2)O)]·6H(2)O. All compounds were tested against the parasite Leishmania major promastigotes for their anti-Leishmanial activity and were further assessed for their toxicity to mammalian cells. The NSAID free acids and their bismuth derivatives show negligible anti-Leishmanial activity at concentrations 1.95 to 250 μg/mL against the promastigotes of L. major whereas in the case of mammalian cells only bismuth complexes of naproxen and mefenamic acid have significant effect at concentration≥250 μg/mL. The bismuth(III) complexes of substituted benzoic acids show significant anti-Leishmanial activity against the promastigotes of L. major V121 at very low concentrations while their respective free carboxylic acids show no effective activity. However, the bismuth compounds inhibit the growth of the mammalian cells at all concentrations studied (1.95 to 500 μg/mL) following 48 h incubation. The comparatively low toxicity of BiCl(3) and Bi(NO(3))(3), suggests that overall toxicity of bismuth complexes towards the parasite is both ligand and metal dependent.
authors.affiliation: School of Chemistry, Monash University, Clayton, Melbourne, Victoria, Australia. phil.andrews@monash.edu
authors.forename: Philip C
authors.initials: PC
authors.lastname: Andrews
authors.forename: Rene
authors.initials: R
authors.lastname: Frank
authors.forename: Peter C
authors.initials: PC
authors.lastname: Junk
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kedzierski
authors.forename: Ish
authors.initials: I
authors.lastname: Kumar
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: MacLellan
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry; D001729:Bismuth / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D002412:Cations; D002478:Cells, Cultured; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000166:cytology / Q000187:drug effects* / Q000469:parasitology; D018320:Leishmania major / Q000166:cytology / Q000187:drug effects / Q000469:parasitology; D007896:Leishmaniasis / Q000188:drug therapy / Q000378:metabolism / Q000469:parasitology; D008528:Mefenamic Acid / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000977:Antiparasitic Agents; D001565:Benzoates; D002264:Carboxylic Acids; D002412:Cations; D009942:Organometallic Compounds; D008528:Mefenamic Acid; D015082:2,2'-Dipyridyl; D001729:Bismuth