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Synthesis and characterization of bismuth(III) and antimony(V) porphyrins: high antileishmanial activity against antimony-resistant parasite

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Abstract

Two bismuth(III) porphyrins—5,10,15,20-tetrakis(phenyl)porphyrinatobismuth(III) nitrate, [Bi(III)(TPP)]NO3, and the unprecedent 5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinatobismuth(III) nitrate, [Bi(III)(T4CMPP)]NO3, and two unprecedented antimony(V) porphyrins dichlorido(5,10,15,20-tetrakis(phenyl)porphyrinato)antimony(V) bromide, [Sb(V)(TPP)Cl2]Br, and dibromido(5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinato)antimony(V) bromide, [Sb(V)(T4CMPP)Br2]Br,—were synthesized by reacting the corresponding porphyrin ligand with Bi(NO3)3·5H2O or SbCl3. All compounds were characterized by UV–vis, 1H 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)Br2]Br was more active against the promastigote form of Sb-resistant mutant strain as compared to the sensitive parental strain, with IC50 in the micromolar range. These data contrasted with those obtained using the Sb(III) drug potassium antimony tartrate, which displayed IC50 of 110 μmol L−1 against the Sb-sensitive parasite and was almost inactive against the Sb-resistant strain. The H2T4CMPP ligand also showed antileishmanial activity against Sb-resistant and -sensitive strains, but with IC50 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)Br2]Br constitutes a new antileishmanial drug candidate.

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Abbreviations

αMEM:

Minimum essential culture medium

BALB/c:

Albino mice

BSS:

Bismuth subsalicylate

CBS:

Bismuth subcitrate

DMF:

N,N-dimethylformamide

FBS:

Fetal calf serum

HEPES:

4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PBS:

Phosphate-buffered saline

Phen:

1,10-Phenanthroline

RPMI:

Roswell Park Memorial Institute (cell culture medium)

TMS:

Tetramethylsilane

TA:

Potassium antimony(III) tartrate

[Bi(III)(TPP)]NO3 :

5,10,15,20-Tetrakis(phenyl)porphyrinatobismuth(III) nitrate

[Bi(III)(T4CMPP)]NO3 :

5,10,15,20-Tetrakis(4-carbomethoxyphenyl)porphyrinatobismuth(III) nitrate

[Sb(V)(TPP)Cl2]Br:

Dichlorido(5,10,15,20-tetrakis(phenyl)porphyrinato)antimony(V) bromide

[Sb(V)(T4CMPP)Br2]Br:

Dibromido(5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinato)antimony(V) bromide

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Acknowledgments

We thank CNPq, CAPES, and FAPEMIG for the financial support.

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Authors and Affiliations

  1. Departamento de Química, ICEx, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil

    Marcela Luísa Gomes, Gilson DeFreitas-Silva, Cynthia Demicheli & Ynara Marina Idemori

  2. Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil

    Priscila Gomes dos Reis & Frédéric Frézard

  3. Departamento de Parasitologia, ICB, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil

    Maria Norma Melo

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  1. Marcela Luísa Gomes
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  3. Priscila Gomes dos Reis
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Correspondence to Ynara Marina Idemori.

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Gomes, M.L., DeFreitas-Silva, G., dos Reis, P.G. et al. Synthesis and characterization of bismuth(III) and antimony(V) porphyrins: high antileishmanial activity against antimony-resistant parasite. J Biol Inorg Chem 20, 771–779 (2015). https://doi.org/10.1007/s00775-015-1264-4

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  • DOI: https://doi.org/10.1007/s00775-015-1264-4

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