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

• Published in: Pharmaceutical biology 2017-01, Vol.55 (1), p.1601-1607
• Main Authors: Araújo-Vilges, Keline Medeiros de, Oliveira, Stefan Vilges de, Couto, Shirley Claudino Pereira, Fokoue, Harold Hilarion, Romero, Gustavo Adolfo Sierra, Kato, Massuo Jorge, Romeiro, Luiz Antonio Soares, Leite, José Roberto Souza Almeida, Kuckelhaus, Selma Aparecida Souza
• Format: Article
• Language: English
• Subjects: Animals; Cell Survival - drug effects; Cinnamates - administration & dosage; Cinnamates - chemistry; Cinnamates - pharmacology; Cytotoxicity; Dose-Response Relationship, Drug; Erythrocytes; Erythrocytes - parasitology; Female; Humans; Immune system; Inhibitory Concentration 50; Leishmania - drug effects; Leishmania amazonensis; Leishmaniasis; Leishmaniasis; Piperaceae; Light microscopy; Malaria; Male; Mice; Peritoneum; Peritoneum - cytology; Peritoneum - drug effects; Piperaceae - chemistry; Piperidones - administration & dosage; Piperidones - isolation & purification; Piperidones - pharmacology; Piperlongumine; Plasmodium falciparum; Plasmodium falciparum - drug effects; Protozoa; selectivity index; Time Factors; Tropical diseases
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2017.1313870

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 (IC 50 ) in L. amazonensis and cytotoxic concentration (CC 50 ) in peritoneal cell were assessed by the MTT method after 6 h of incubation, while the IC 50 for P. falciparum-infected erythrocytes was determined by optical microscopy after 48 or 72 h of incubation; the Selectivity Index (SI) was calculated by CC 50 /IC 50 . Results: All compounds inhibited the growth of microorganisms, being more effective against P. falciparum after 72 h of incubation, especially for the compounds 1 (IC 50  = 3.2 μg/mL) and 5 (IC 50  = 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 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.