Antiproliferative activity and conversion of tachyzoite to bradyzoite of Toxoplasma gondii promoted by new zinc complexes containing sulfadiazine?

RSC Advances Pub Date: 2015-11-18 DOI: 10.1039/C5RA17690E

Abstract

Here we describe the synthesis and biological effect against Toxoplasma gondii of two new zinc complexes containing sulfadiazine: [(SDZ)Zn(μ-BPA)2Zn(SDZ)] 1 and [Zn(SDZ)(HSDZ)(Cl)(OH2)] 2, where SDZ is the anion sulfadiazine. The complexes were characterized by elemental analysis, IR, 1H NMR, UV-Vis, electrospray ionization ESI(+)-MS and tandem mass spectrometry ESI(+)-MS/MS. X-ray diffraction studies were performed for complex 1 revealing the presence of sulfadiazine molecules coordinated to the metal center, resulting in a dinuclear complex. The cytotoxic effects of both complexes on T. gondii infected LLC-MK2 host cells are presented and indicate that both reduced the growth of T. gondii in this cell. After 48 h of treatment, both compounds induced the formation of pseudocysts confirmed by fluorescence microscopy performed with Dolichos biflorus lectin, a cystic wall marker. Pseudocysts were not observed in untreated cells or after treatment with NaSDZ alone. These results suggest the effect of the metal and the ligand on the anti-toxoplasma activity. In silico molecular pharmacokinetics studies indicate poor permeability and oral bioavailability exhibited by complex 1. As complex 1 presents better antitoxoplasma activity than SDZ we suggest that complex 1 could be acting by a distinct mode of action compared to SDZ which until now was unclear.

Graphical abstract: Antiproliferative activity and conversion of tachyzoite to bradyzoite of Toxoplasma gondii promoted by new zinc complexes containing sulfadiazine
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