Anti-leishmanial activity of novel homo- and heteroleptic bismuth(III) thiocarboxylates

Journal Publication ResearchOnline@JCU
Andrews, Philip C.;Junk, Peter C.;Kedzierski, Lukasz;Peiris, Roshani
Abstract

Two new thiocarboxylic acids, p-bromothiobenzoic BTA and thionaphthoic acid TNA, and five new homo-and heteroleptic bismuth(III) compounds derived from thiocarboxylic acids: [Bi{S(C=O)C₆H₄Br}₃] 1, [PhBi{S(C=O) C₆H₄Br}₂] 2, [Bi{S(C=O)C₁₀H₇}₃] 3, [PhBi{S(C=O)C₁₀H₇}₂] 4, and [Ph₂Bi{S(C=O)C₁₀H₇}] 5 were synthesised and fully characterised. The solid-state structure of complex [PhBi{S(C=O)C₆H₄Br}₂] 2 was confirmed by X-ray crystallography. In complex 2, the two thiocarboxylate ligands are coordinated to the bismuth(III) centre in a didentate fashion, forming a distorted octahedral geometry in which the phenyl group and the lone pair are oriented axial to the plane formed by the two thiocarboxylate ligands. Long-range Bi-S interactions (3.54 angstrom) link these monomeric units to form a one-dimensional polymer. These compounds, in addition to six previously synthesised complexes: [Bi{SC(=O)C₆H₅}₃] 6, [PhBi{SC(=O)C₆H₅}₂] 7, [Ph₂Bi{SC(=O)C₆H₅}] 8, [Bi{SC(=O)C₆H₄NO₂}₃] 9, [PhBi{SC(=O)C₆H₄NO₂}₂)] 10, and [PhBi{SC(=O)C₆H₄SO₃}] 11, and the thiocarboxylic acids themselves, were assessed for their in vitro activity against Leishmania major promastigotes, and for general toxicity against human fibroblast cells. The thiocarboxylic acids, with the exception of thiobenzoic acid and sulfothiobenzoic acid, were toxic to both L. major parasites and the mammalian cells at high concentrations of 50-100 mu M. The bismuth(III) thiocarboxylate derivatives proved to be more active than the corresponding acids. Among these, the heteroleptic phenyl-substituted bismuth(III) complexes 2, 4, 5, and 7 were highly active, showing IC₅₀ (half maximal inhibitory concentration) values ranging from 0.39 to 4.69 mu M, and a clear ligand dependence on activity.

Journal

Australian Journal of Chemistry

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Volume

66

ISBN/ISSN

1445-0038

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Issue

10

Pages Count

9

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Publisher

CSIRO Publishing

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DOI

10.1071/CH13374