1. Synthesis and characterization of bismuth(III) and antimony(V) porphyrins: high antileishmanial activity against antimony-resistant parasite.
- Author
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Gomes, Marcela, DeFreitas-Silva, Gilson, Reis, Priscila, Melo, Maria, Frézard, Frédéric, Demicheli, Cynthia, and Idemori, Ynara
- Subjects
BISMUTH compounds ,CHEMICAL synthesis ,ANTIMONY ,PORPHYRINS ,LEISHMANIA ,PARASITES ,THERAPEUTICS - Abstract
Two bismuth(III) porphyrins-5,10,15,20-tetrakis(phenyl)porphyrinatobismuth(III) nitrate, [Bi(III)(TPP)]NO, and the unprecedent 5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinatobismuth(III) nitrate, [Bi(III)(T4CMPP)]NO, and two unprecedented antimony(V) porphyrins dichlorido(5,10,15,20-tetrakis(phenyl)porphyrinato)antimony(V) bromide, [Sb(V)(TPP)Cl]Br, and dibromido(5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinato)antimony(V) bromide, [Sb(V)(T4CMPP)Br]Br,-were synthesized by reacting the corresponding porphyrin ligand with Bi(NO)·5HO or SbCl. All compounds were characterized by UV-vis, H NMR spectroscopy, and mass spectrometry. The new compounds were also characterized by elemental analysis. Because antimony and bismuth compounds have been widely applied in medicine, the activity of these complexes was tested against Sb-sensitive and -resistant Leishmania amazonensis parasites. [Sb(V)(T4CMPP)Br]Br was more active against the promastigote form of Sb-resistant mutant strain as compared to the sensitive parental strain, with IC in the micromolar range. These data contrasted with those obtained using the Sb(III) drug potassium antimony tartrate, which displayed IC of 110 μmol L against the Sb-sensitive parasite and was almost inactive against the Sb-resistant strain. The HT4CMPP ligand also showed antileishmanial activity against Sb-resistant and -sensitive strains, but with IC at least tenfold greater than that of the complex. The Sb(V)-porphyrin complex was also active against intracellular amastigotes and showed a higher selectivity index than the conventional Sb(V) drug glucantime, in both Sb-sensitive and -resistant strains. The greater antileishmanial activity of this complex could be attributed to an increased cellular uptake of Sb. Thus, [Sb(V)(T4CMPP)Br]Br constitutes a new antileishmanial drug candidate. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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