The potent cell permeable calpain inhibitor MDL28170 affects the interaction of Leishmania amazonensis with macrophages and shows anti-amastigote activity

- The calpain inhibitor MDL28170 effects were evaluated against Leishmania amazonensis.
- MDL28170 reduced the interaction of promastigotes with mammalian macrophages.
- MDL28170 was able to decrease the infection rate in macrophages.
- Treatment with MDL28170 did not alter the nitric oxide production by macrophages.
- Production of TNF-α was raised in MDl28170-treated, infected macrophages.

Since the discovery of the28 first drugs used in leishmaniasis treatment up to now, the search for compounds with anti-Leishmania activity without toxic effects and able to overcome the emergency of resistant strains remains a major goal to combat this neglected disease. With this in mind, in the present work, we evaluated the effects of the calpain inhibitor MDL28170 on the interaction process of Leishmania amazonensis promastigote forms with murine peritoneal macrophages and on the intracellular amastigotes. Our results showed that the calpain inhibitor MDL28170 at 15 and 30 μM significantly reduced the interaction process of promastigotes with macrophages by 16% and 41%, respectively. The inhibitor was also able to drastically reduce the number of infected macrophages in a time- and dose-dependent manner: after only 24 h, MDL28170 was able to significantly diminish the infection rate, presenting an IC50 value of 18.2 μM for amastigotes. The treatment with MDL28170 did not alter the nitric oxide production, but the production of TNF-α was significantly raised. Altogether, the results presented here contribute to the search of new proteolytic inhibitors able to act in a selective and effective manner against the diseases caused by trypanosomatids.

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