Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters











Database
Language
Publication year range
1.
Drug Dev Res ; 85(3): e22194, 2024 May.
Article in English | MEDLINE | ID: mdl-38704828

ABSTRACT

The aim the present study was to investigate the impact of novel pentavalent organobismuth and organoantimony complexes on membrane integrity and their interaction with DNA, activity against Sb(III)-sensitive and -resistant Leishmania strains and toxicity in mammalian peritoneal macrophages. Ph3M(L)2 type complexes were synthesized, where M = Sb(V) or Bi(V) and L = deprotonated 3-(dimethylamino)benzoic acid or 2-acetylbenzoic acid. Both organobismuth(V) and organoantimony(V) complexes exhibited efficacy at micromolar concentrations against Leishmania amazonensis and L. infantum but only the later ones demonstrated biocompatibility. Ph3Sb(L1)2 and Ph3Bi(L1)2 demonstrated distinct susceptibility profiles compared to inorganic Sb(III)-resistant strains of MRPA-overexpressing L. amazonensis and AQP1-mutated L. guyanensis. These complexes were able to permeate the cell membrane and interact with the Leishmania DNA, suggesting that this effect may contribute to the parasite growth inhibition via apoptosis. Taken altogether, our data substantiate the notion of a distinct mechanism of uptake pathway and action in Leishmania for these organometallic complexes, distinguishing them from the conventional inorganic antimonial drugs.


Subject(s)
Antimony , Antiprotozoal Agents , Cell Membrane , Drug Resistance , Organometallic Compounds , Antimony/pharmacology , Antimony/chemistry , Animals , Organometallic Compounds/pharmacology , Mice , Cell Membrane/drug effects , Antiprotozoal Agents/pharmacology , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/parasitology , Leishmania/drug effects , DNA, Protozoan , Leishmania infantum/drug effects , Leishmania infantum/genetics , Mice, Inbred BALB C
SELECTION OF CITATIONS
SEARCH DETAIL