TY - JOUR
T1 - In vitro toxicity of palladium(II) and gold(III) porphyrins and their aqueous metal ion counterparts on Trypanosoma brucei brucei growth
AU - Nyarko, Elvis
AU - Hara, Tatsuru
AU - Grab, Dennis J.
AU - Habib, Ahsan
AU - Kim, Yuri
AU - Nikolskaia, Olga
AU - Fukuma, Toshihide
AU - Tabata, Masaaki
PY - 2004/6/30
Y1 - 2004/6/30
N2 - The trypanocidal effects of aqueous gold(III) and palladium(II) and their metalloporhyrin derivatives on Trypanosoma brucei brucei growth in culture have been studied using an Alamar Blue indicator assay. All the experiments were conducted in the dark. As previously described for mercury(II), cadmium(II) and lead(II) porphyrins [Chem.-Biol. Interact. 139 (2002) 177], the toxicity of the metalloporphyrin complex of palladium(II) to T. b. brucei parasites was much higher compared to the aqueous free palladium(II) and free base porphyrin. Palladium(II) porphyrin, free palladium(II), and the free base porphyrin were trypanocidal to T. b. brucei at concentrations >1.5×10-6, >6.1×10-6 and >1.9×10-5 M, respectively. While gold(III) porphyrin was effective against the parasites at concentrations >4.8×10-6 M, its aqueous gold(III) was toxic at concentrations as low as 2.0×10-7 M due to the generation of free radicals in the presence of this metal ion which enhanced its toxicity to the T. b. brucei parasites. Although some cell division was observed in some of the cells treated with palladium(II) porphyrin, some dividing cells had no nucleus due to unequal division and delivery of the nuclei into the daughter cells. As a result, the rate of cell division decreased with time and cell death occurred within 24 h. Interestingly, trypanosomes treated with metalloporphyrin complexes displayed different morphological features from those cells treated with free base porphyrin or metal ions. Of all the porphyrins and free metal ions tested, only mercury(II) porphyrin and aqueous gold(III) ion were toxic to the trypanosomes in the 10-7 M range. The chemotherapeutic potential of these observations is discussed.
AB - The trypanocidal effects of aqueous gold(III) and palladium(II) and their metalloporhyrin derivatives on Trypanosoma brucei brucei growth in culture have been studied using an Alamar Blue indicator assay. All the experiments were conducted in the dark. As previously described for mercury(II), cadmium(II) and lead(II) porphyrins [Chem.-Biol. Interact. 139 (2002) 177], the toxicity of the metalloporphyrin complex of palladium(II) to T. b. brucei parasites was much higher compared to the aqueous free palladium(II) and free base porphyrin. Palladium(II) porphyrin, free palladium(II), and the free base porphyrin were trypanocidal to T. b. brucei at concentrations >1.5×10-6, >6.1×10-6 and >1.9×10-5 M, respectively. While gold(III) porphyrin was effective against the parasites at concentrations >4.8×10-6 M, its aqueous gold(III) was toxic at concentrations as low as 2.0×10-7 M due to the generation of free radicals in the presence of this metal ion which enhanced its toxicity to the T. b. brucei parasites. Although some cell division was observed in some of the cells treated with palladium(II) porphyrin, some dividing cells had no nucleus due to unequal division and delivery of the nuclei into the daughter cells. As a result, the rate of cell division decreased with time and cell death occurred within 24 h. Interestingly, trypanosomes treated with metalloporphyrin complexes displayed different morphological features from those cells treated with free base porphyrin or metal ions. Of all the porphyrins and free metal ions tested, only mercury(II) porphyrin and aqueous gold(III) ion were toxic to the trypanosomes in the 10-7 M range. The chemotherapeutic potential of these observations is discussed.
KW - Gold(II) porphyrin
KW - Palladium(II) porphyrin
KW - Trypanosoma brucei brucei
UR - http://www.scopus.com/inward/record.url?scp=3042653086&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042653086&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2004.03.004
DO - 10.1016/j.cbi.2004.03.004
M3 - Article
C2 - 15223353
AN - SCOPUS:3042653086
SN - 0009-2797
VL - 148
SP - 19
EP - 25
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
IS - 1-2
ER -