title: In vitro and in vivo activity of new rhodium (III) complexes against Leishmania donovani.
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.
authors.affiliation: Departamento de Bioquímica y Parasitología Molecular, Instituto de Biotecnología, Facultad de Ciencias, Universidad de Granada, España.
authors.forename: M N
authors.initials: MN
authors.lastname: Rodriguez-Cabezas
authors.forename: C M
authors.initials: CM
authors.lastname: Mesa-Valle
authors.forename: S
authors.initials: S
authors.lastname: Azzouz
authors.forename: V
authors.initials: V
authors.lastname: Moraleda-Lindez
authors.forename: D
authors.initials: D
authors.lastname: Craciunescu
authors.forename: M T
authors.initials: MT
authors.lastname: Gutierrez-Rios
authors.forename: M I
authors.initials: MI
authors.lastname: De Frutos
authors.forename: A
authors.initials: A
authors.lastname: Osuna
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D066298:In Vitro Techniques; D007893:Leishmania donovani / Q000187:drug effects* / Q000469:parasitology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008647:Mesocricetus; D051381:Rats; D017208:Rats, Wistar; D012238:Rhodium / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D012238:Rhodium