In vitro and in vivo activity of new rhodium (III) complexes against Leishmania donovani |
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Authors: | Rodriguez-Cabezas M N Mesa-Valle C M Azzouz S Moraleda-Lindez V Craciunescu D Gutierrez-Rios M T De Frutos M I Osuna A |
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Affiliation: | Departamento de Bioquímica y Parasitología Molecular, Instituto de Biotecnología, Facultad de Ciencias, Universidad de Granada, Espa?a. |
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Abstract: | The activities of 17 new rhodium drug complexes were determined against Leishmania donovani promastigotes. The five most active salts were selected: [Rh(III)(2-amino-6-ethoxybenzothiazole)(4)Br(2)](+)Br(-); [Rh(III)(2-bromothiazole)(4)(Br)(2)](+)Br(-); [Rh(III)(mefloquine)(4)(Cl)(2)](+)Cl(-); [Rh(III)(2-mepacrine)(4)(Cl)(2)](+)Cl(-), and [Rh(III)(oxamniquine)(4)(Cl)(2)](+)Cl(-), which induced growth-inhibition rates of more than 50% at 24 h of treatment and at the maximum dosage tested. The cytotoxicity assays on the macrophage cell line J-774 showed high cytotoxicity for the salts [Rh(III) (mefloquine)(4)(Cl)(2)](+)Cl(-), [Rh(III)(2-mepacrine)(4)(Cl)(2)](+)Cl(-) and [Rh(III)(oxaminquine)(4)(Cl)(2)](+)Cl(-) with a percentage of specific (15)Cr release of 49.3, 64.8 and 53.2% at 24 h of incubation and 100 microg/ml. Meanwhile, assays of the other compounds showed practically no cytotoxicity. The ultrastructural studies in the flagellates treated with the salt [Rh(III)(2-amino-6-ethoxybenzothiazole)(4)Br(2)](+)Br(-) showed some alterations in the nucleus of the parasites with a very condensed chromatin and an electrodense endosome. This compound showed a high in vivo activity in parasitized Wistar rats. |
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