Jornal de Doenças Tropicais e Saúde Pública

Abstrato

Preliminary Results Indicate the Anti-Proliferative Effect of HIV-1 Protease Inhibitors on Trypanosoma brucei Cells can be Due to the Non-Specific Targeting of Metallo-and Cysteine-Proteases

Netsanet Worku and Gerd Birkenmeier

Background: Initial studies have confirmed the efficacy of protease inhibitors in the treatment of Trypanosoma cruzi, Plasmodium falciparum, and Leishmania major. However, studies on efficacy and specific protease inhibition of HIV-1 protease inhibitors on Trypanosoma brucei cells remained untouched. The objective of the current study was to determine the efficacy of two HIV-1 protease inhibitors, ritonavir, and saquinavir, in Trypanosoma brucei proliferation and to determine if these HIV-1 protease inhibitors target the activity of the Trypanosoma brucei major proteases.

Methods: Time dependency test at variable increasing concentrations, motile cell counts, alamarBlue^® cell proliferation/viability assay and zymography were among the methods applied.

Results: Both ritonavir (IC₅₀=12.23 ± 0.33 µM) and saquinavir (IC₅₀=11.49 ± 0.31 µM) effectively inhibited Trypanosoma brucei cells proliferation. The major proteases identified in these cells were the cysteine (~29 kDa Mr) and metallo- (~66 kDa Mr) proteases. Protein band densitometry results showed a statistically significant (Pvalue< 0.05) inhibition in metallo-and cysteine-proteases’ activity in Trypanosoma brucei cells.

Conclusion: The results suggest that RTV and SQV showed an anti-proliferative effect in Trypanosoma brucei cells possibly due to the non-specific targeting of the cysteine-and metalloprotease activities of the parasite.