Anti-leishmanial activity of heteroleptic organometallic Sb(v) compounds.
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.
Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Pakistan.
Muhammad Irshad
MI
Ali
Muhammad Khawar
MK
Rauf
Amin
A
Badshah
Ish
I
Kumar
Craig M
CM
Forsyth
Peter C
PC
Junk
Lukasz
L
Kedzierski
Philip C
PC
Andrews
D000965:Antimony / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D018320:Leishmania major / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D000965:Antimony