Anti-leishmanial activity of heteroleptic organometallic Sb(v) compounds

Journal Publication ResearchOnline@JCU
Ali, Muhammad;Rauf, Muhammad;Badshah, Amin;Kumar, Ish;Forsyth, Craig M.;Junk, Peter C.;Kedzierski, Lukasz;Andrews, Philip C.
Abstract

In seeking new drugs for the treatment of the parasitic disease Leishmaniasis, an extensive range of organometallic antimony(V) dicarboxylates of the form [SbR₃(O2CR')2] have been synthesised, characterised and evaluated. The organometallic moieties (R) in the complexes vary in being Ph, tolyl (o, m or p), or benzyl. The carboxylates are predominantly substituted benzoates with some compounds incorporating acetato or cinnamato ligands. The crystal structures of [Sb(p-Tol)₃(O₂CC₆H₂-3,4,5-(OMe)₃)₂]·0.5PhMe and [SbPh₃(m-CH₃C₆H₄CH₂CO₂)₂] were determined and shown to adopt a typical trigonal pyramidal geometry, being monomeric with a five coordinate Sb centre. In total, the biological activity of 26 Sb(V) compounds was assessed against the Leishmania major parasite, and also human fibroblast skin cells to give a measure of general toxicity. Of these, 11 compounds (predominantly substituted benzoates with m- or p-tolyl ligands) proved to be highly effective against the parasite amastigotes at concentrations of 0.5–3.5 µM, while being non-toxic towards the mammalian cells at levels below 25 μM, making them highly promising drug candidates.

Journal

Dalton Transactions

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Volume

42

ISBN/ISSN

1477-9234

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Issue

48

Pages Count

9

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Publisher

Royal Society of Chemistry

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DOI

10.1039/c3dt51382c