Synthesis, characterization and antileishmanial studies of some bioactive heteroleptic pentavalent antimonials

Abstract

In pursuit of safe drug candidates for the treatment of parasitic diseases like leishmaniasis, a series of heteroleptic pentavalent antimonials of the type [R 3 Sb(O 2 CR′) 2 ] ( 1 – 9 ) have been synthesized and characterized using elemental analysis (CHN), Fourier transform infrared spectroscopy and multinuclear ( 1 H and 13 C) NMR spectroscopy. The carboxylates studied are predominantly substituted benzoates with some complexes having acetato or nicotinato ligands. The crystal structures of [Sb(C 6 H 5 ) 3 ( o ‐NH 2 C 6 H 4 COO) 2 ] ( 1 ) and [Sb(C 6 H 5 ) 3 (3,5‐Cl 2 C 6 H 3 COO) 2 ] ( 4 ) were determined as essentially monomeric with an Sb(V) centre and shown to adopt geometries intermediate between trigonal bipyramidal and square pyramidal. The antileishmanial activity was assessed against Leishmania tropica KWH23, and also human macrophages were used to measure the cytotoxicity of these complexes. The IC 50 of the antimonials 1 – 9 indicates their efficaciousness as compared with the standard antimonial drug used. The significant activity of complex 1 assumes that greater multitude of interactions is the cause of enhanced antileishmanial activity. Cytotoxicity results showed that these antimonials are highly active even at low concentrations and are biocompatible with human macrophages, making them promising drug candidates for further investigations in this field.