Improved antileishmanial activity of Dppz through complexation with antimony(III) and bismuth(III): investigation of the role of the metal
| Autor: | Priscila G. Reis, Rubens L. Monte-Neto, Edgar H. Lizarazo-Jaimes, Maria Norma Melo, Nelson G. Fernandes, Cynthia Demicheli, Frédéric Frézard, Nivaldo L. Speziali |
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| Rok vydání: | 2012 |
| Předmět: |
Antimony
crystal structure Stereochemistry Phenazine dipyrido [3 2-a:2' 3'-c] phenazine antimony bismuth Leishmania drug resistance Pharmaceutical Science chemistry.chemical_element Crystal structure Tartrate Article Analytical Chemistry lcsh:QD241-441 Metal chemistry.chemical_compound Inhibitory Concentration 50 Mice lcsh:Organic chemistry Coordination Complexes Drug Discovery parasitic diseases Spectroscopy Fourier Transform Infrared Animals Physical and Theoretical Chemistry Cytotoxicity Cells Cultured biology Molecular Structure Ligand Organic Chemistry biology.organism_classification Trypanocidal Agents chemistry Chemistry (miscellaneous) visual_art visual_art.visual_art_medium Macrophages Peritoneal Molecular Medicine Phenazines |
| Zdroj: | Molecules Molecules; Volume 17; Issue 11; Pages: 12622-12635 Molecules, Vol 17, Iss 11, Pp 12622-12635 (2012) |
| ISSN: | 1420-3049 |
| Popis: | Two novel trivalent antimony(III) and bismuth(III) complexes with the nitrogen-donor heterocyclic ligand dipyrido[3,2-a:2',3'-c]phenazine (dppz) were synthesized and characterized as [Sb(dppz)Cl3]∙H2O∙CH3OH and [Bi(dppz)Cl3]. The crystal structure of Sb(III) complex was determined by X-ray crystallography. These complexes were evaluated for their activity against the promastigote form of Sb(III)-sensitive and –resistant Leishmania infantum chagasi and Leishmania amazonensis strains. Both complexes were more effective than dppz alone in inhibiting the growth of Leishmania promastigotes and were at least 77 and 2,400 times more active than potassium antimonyl tartrate in Sb(III)-sensitive and -resistant Leishmania, respectively. The cytotoxicity of dppz and its complexes against mouse peritoneal macrophages occurred at dppz concentrations at least 6-fold greater than those found to be active against Leishmania promastigotes.To investigate the role of the metal in the improved antileishmanial activity of dppz, the activity of the Sb(III) complex was compared between the Sb-resistant mutants and their respective parental sensitive strains. The lack of cross-resistance to the Sb(III)-dppz complex together with the much lower activity of antimonyl tartrate, SbCl3 and BiCl3 strongly support the model that the metal is not active by itself but improves the activity of dppz through complexation. |
| Databáze: | OpenAIRE |
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