Toxic effects of mercury(II), cadmium(II) and lead(II) porphyrins on Trypanosoma brucei brucei growth.
The effects of free mercury(II), cadmium(II) and lead(II) ions and their metalloporphyrin-derivatives on Trypanosoma brucei brucei growth in culture were studied. All experiments were conducted in the dark. IC(50) values on growth obtained in 24-h time-course experiments were 1.5 x 10(-7), 2.4 x 10(-6), 4.4 x 10(-6) and 2.6 x 10(-5) M for mercury(II) porphyrin, cadmium(II) porphyrin, lead(II) porphyrin and free base porphyrin, respectively. While the IC50 values for Hg2+, Cd2+ and Pb2+ were 3.6 x 10(-6), 1.5 x 10(-5) and 1.6 x 10(-5) M, respectively. These results clearly indicate that the toxicity of the metalloporphyrin complexes of mercury(II), cadmium(II) and lead(II) to T. b. brucei parasites was much higher compared to their free metal ions and free base porphyrin at low concentrations. It was also observed after 8 h incubation that the metalloporphyrins were effective in inhibiting the division of the parasites at concentrations >1.25 x 10(-7) M for mercury(II) porphyrin, concentrations >1.2 x 10(-6) M for cadmium(II) and lead(II) porphyrins and at concentrations >3.6 x 10(-6) M for Hg2+ ion. These observations were not detected in samples treated with the free metal ions and the free base porphyrin at the same concentrations. Interestingly, trypanosomes treated with metalloporphyrin complexes displayed different morphological features from those cells treated with free base porphyrin or metal ions. The chemotherapeutic potential of the metalloporphyrins of H2TMPyP for treatment of African trypanosomiasis is discussed.
Nyarko
Elvis
E
Department of Chemistry, Faculty of Science and Engineering, Saga University, 1 Honjo-machi, Saga 840-8502, Japan.
Hara
Tatsuru
T
Grab
Dennis J
DJ
Tabata
Masaaki
M
Fukuma
Toshihide
T
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000633:toxicity*; D066298:In Vitro Techniques; D007854:Lead / Q000633:toxicity*; D008018:Life Cycle Stages / Q000187:drug effects; D008136:Longevity / Q000187:drug effects; D008628:Mercury / Q000633:toxicity*; D008665:Metalloporphyrins / Q000633:toxicity*; D014344:Trypanocidal Agents; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development
D006131:Growth Inhibitors; D008665:Metalloporphyrins; D014344:Trypanocidal Agents; D002104:Cadmium; D007854:Lead; D008628:Mercury