Effect of piplartine and cinnamides on Leishmania amazonensis, Plasmodium falciparum and on peritoneal cells of Swiss mice

Abstract

Context: Plants of the Piperaceae family produce piplartine that was used to synthesize the cinnamides.

Objective: To assess the effects of piplartine (1) and cinnamides (2–5) against the protozoa responsible for malaria and leishmaniasis, and peritoneal cells of Swiss mice.

Materials and methods: Cultures of Leishmania amazonensis, Plasmodium falciparum-infected erythrocytes, and peritoneal cells were incubated, in triplicate, with different concentrations of the compounds (0 to 256 μg/mL). The inhibitory concentration (IC₅₀) in L. amazonensis and cytotoxic concentration (CC₅₀) in peritoneal cell were assessed by the MTT method after 6 h of incubation, while the IC₅₀ for P. falciparum-infected erythrocytes was determined by optical microscopy after 48 or 72 h of incubation; the Selectivity Index (SI) was calculated by CC₅₀/IC₅₀.

Results: All compounds inhibited the growth of microorganisms, being more effective against P. falciparum after 72 h of incubation, especially for the compounds 1 (IC₅₀ = 3.2 μg/mL) and 5 (IC₅₀ = 6.6 μg/mL), than to L. amazonensis (compound 1 = 179.0 μg/mL; compound 5 = 106.0 μg/mL). Despite all compounds reducing the viability of peritoneal cells, the SI were <10 to L. amazonensis, whereas in the cultures of P. falciparum the SI >10 for the piplartine (>37.4) and cinnamides 4 (>10.7) and 5 (= 38.4).

Discussion and conclusion: The potential of piplartine and cinnamides 4 and 5 in the treatment of malaria suggest further pre-clinical studies to evaluate their effects in murine malaria and to determine their mechanisms in cells of the immune system.

Keywords:

• Piperlongumine
• selectivity index
• malaria
• Leishmaniasis; Piperaceae

Acknowledgements

We are grateful to Renata Ribeiro de Sousa and Tainan Ribeiro, for excellent technical assistance, to Lucas Souza Kuckelhaus, for reviewing the English language of the manuscript, and to CAPES/Ministry of Education/Brazil for the financial support.

Disclosure statement

The authors declare no conflict to interests.