A structural investigation of heteroleptic pentavalent antimonials and their leishmanicidal activity

作者：Mushtaq Rabia; Rauf Muhammad Khawar^*; Bond Marcus; Badshah Amin^*; Ali Muhammad Irshad; Nadhman Akhtar; Yasinzai Masoom; Tahir Muhammad Nawaz

来源：Applied Organometallic Chemistry, 2016, 30(6): 465-472.

DOI：10.1002/aoc.3456

• pentavalent antimonials
• Leishmania tropica KWH23
• leishmanicidal
• cytotoxicity

In the quest for new drug candidates for the safe treatment of parasitic diseases like leishmaniasis, a series of heteroleptic pentavalent antimonials of the type [SbR3(OOCR')(2)] were synthesized and characterized using elemental analysis, Fourier transform infrared spectroscopy and multinuclear (H-1 and C-13) NMR spectroscopy. The carboxylate moieties are predominantly substituted benzoates with some complexes that fit in acetato or nicotinato ligands. The crystal structures of [Sb(p-Tol)(3)(p-CH3C6H4COO)(2)], [Sb(p-Tol)(3)(3,5-Cl2C6H3COO)(2)] and [Sb(p-Tol)(3)(3-nicotinato)(2)] were determined crystallographically and shown to adopt geometries intermediate between trigonal bipyramidal and square pyramidal, and essentially monomeric with a five-coordinated Sb center. The leishmanicidal activity was assessed against the Leishmania tropica KWH23 parasite, and the cytotoxicity level was also measured on human macrophage blood cells. It was observed that IC50 of the antimonials was 100-fold superior as compared with the standard antimonial drug used. Cytotoxicity results showed that these antimonials are highly active even at low concentrations and are biocompatible with human macrophages, making them highly promising drug candidates for further investigation.

• 出版日期2016-6