caa a22 4500 605507708 CHVBK 20210128100633.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00775-015-1264-4 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1264-4 Synthesis and characterization of bismuth(III) and antimony(V) porphyrins: high antileishmanial activity against antimony-resistant parasite [Elektronische Daten] [Marcela Gomes, Gilson DeFreitas-Silva, Priscila dos Reis, Maria Melo, Frédéric Frézard, Cynthia Demicheli, Ynara Idemori] 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 110μmol 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. SBIC, 2015 Antimony(V) porphyrins nationallicence Bismuth(III) porphyrins nationallicence Leishmania nationallicence αMEM : Minimum essential culture medium nationallicence BALB/c : Albino mice nationallicence BSS : Bismuth subsalicylate nationallicence CBS : Bismuth subcitrate nationallicence DMF : N,N-dimethylformamide nationallicence FBS : Fetal calf serum nationallicence HEPES : 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid nationallicence MTT : 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide nationallicence PBS : Phosphate-buffered saline nationallicence Phen : 1,10-Phenanthroline nationallicence RPMI : Roswell Park Memorial Institute (cell culture medium) nationallicence TMS : Tetramethylsilane nationallicence TA : Potassium antimony(III) tartrate nationallicence [Bi(III)(TPP)]NO3 : 5,10,15,20-Tetrakis(phenyl)porphyrinatobismuth(III) nitrate nationallicence [Bi(III)(T4CMPP)]NO3 : 5,10,15,20-Tetrakis(4-carbomethoxyphenyl)porphyrinatobismuth(III) nitrate nationallicence [Sb(V)(TPP)Cl2]Br : Dichlorido(5,10,15,20-tetrakis(phenyl)porphyrinato)antimony(V) bromide nationallicence [Sb(V)(T4CMPP)Br2]Br : Dibromido(5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinato)antimony(V) bromide nationallicence Gomes Marcela Departamento de Química, ICEx, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut DeFreitas-Silva Gilson Departamento de Química, ICEx, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut dos Reis Priscila Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut Melo Maria Departamento de Parasitologia, ICB, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut Frézard Frédéric Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut Demicheli Cynthia Departamento de Química, ICEx, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut Idemori Ynara Departamento de Química, ICEx, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 771-779 0949-8257 20:5<771 2015 20 775 https://doi.org/10.1007/s00775-015-1264-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1264-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gomes Marcela Departamento de Química, ICEx, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut NATIONALLICENCE 700 1- DeFreitas-Silva Gilson Departamento de Química, ICEx, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut NATIONALLICENCE 700 1- dos Reis Priscila Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut NATIONALLICENCE 700 1- Melo Maria Departamento de Parasitologia, ICB, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut NATIONALLICENCE 700 1- Frézard Frédéric Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut NATIONALLICENCE 700 1- Demicheli Cynthia Departamento de Química, ICEx, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut NATIONALLICENCE 700 1- Idemori Ynara Departamento de Química, ICEx, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 771-779 0949-8257 20:5<771 2015 20 775