Development of new combination anti-leishmanial complexes: Triphenyl Sb(V) mono-hydroxy mono-quinolinolates.

In seeking to develop single entity combination anti-Leishmanial complexes six heteropletic organometallic Sb(V) hydroxido quinolinolate complexes of general formula [SbPh 3 (C 9 H 4 NORR')(OH)] have been synthesised and characterised, derived from a series of halide substituted quinolinols (8-hydroxyquinolines). Single crystal X-ray diffraction on all the complexes show a common distorted six-coordinate octahedral environment at the Sb(V) centre, with the aryl groups and nitrogen atom of quinolinolate ligand bonding in the equatorial planes, with the two oxygen atoms (hydroxyl and quinolinolate) occupying the axial plane in an almost linear configuration. Each complex was tested for their anti-promastigote activity and mammalian cytotoxicity and a selectivity indices established. The complexes displayed excellent anti-promastigote activity (IC 50 : 2.03–3.39 μM) and varied mammalian cytotoxicity (IC 50 : 12.7–46.9 μM), leading to a selectivity index range of 4.52–16.7. All complexes displayed excellent anti-amastigote activity with a percentage infection range of 2.25%–9.00%. All complexes performed substantially better than the parent quinolinols and comparable carboxylate complexes [SbPh 3 (O 2 CRR') 2 ] indicating the synergistic role of the Sb(V) and quinolinol moieties in increasing parasite mortality. Two of the complexes [SbPh 3 (C 9 H 4 NOBr 2)(OH)] 4, [SbPh 3 (C 9 H 4 NOI 2)(OH)] 5, provide an ideal combination of high selective and good activity towards the leishmanial amastigotes and offer the potential as good lead compounds. [Display omitted] • Potential single entity anti-leishmanial combination drugs combining Sb(V) and quinolinols have been designed and synthesised. • The organometallic Sb(V) quinolinolato complexes show enhanced activity and good selectivity towards Leishmania. • The complexes display good selectivity indices having low mammalian cell toxicity. • Comparison with analogous Sb(V) carboxylates highlights the synergy of the quinolinolate ligands with aryl-Sb(V) moieties. [ABSTRACT FROM AUTHOR]