Leishmanicidal Effects of Piperlongumine (Piplartine) and Its Putative Metabolites

• Published in: Planta medica Vol. 84; no. 15; p. 1141
• Main Authors: Moreira, Fernanda de Lima, Riul, Thalita Bachelli, Moreira, Marcela de Lima, Pilon, Alan Cesar, Dias-Baruffi, Marcelo, Araújo, Márcio S S, Lopes, Norberto Peporine, de Oliveira, Anderson R M
• Format: Journal Article
• Language: English
• Published: Germany 01-10-2018
• Subjects: Animals; Anthelmintics - chemistry; Anthelmintics - pharmacology; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Biomimetics; Dioxolanes - chemistry; Dioxolanes - pharmacology; Female; Inhibitory Concentration 50; Leishmania infantum - drug effects; Liver - drug effects; Macrophages, Peritoneal - drug effects; Metalloporphyrins - metabolism; Mice, Inbred BALB C; Microsomes; Piperaceae - chemistry; Piperidones - chemistry; Piperidones - pharmacology; Rats
• ISSN: 1439-0221
• DOI: 10.1055/a-0614-2680

Piperlongumine is an amide alkaloid found in Piperaceae species that shows a broad spectrum of biological properties, including antitumor and antiparasitic activities. Herein, the leishmanicidal effect of piperlongumine and its derivatives produced by a biomimetic model using metalloporphyrins was investigated. The results showed that IC
values of piperlongumine in promastigote forms of
and
were 7.9 and 3.3 µM, respectively. The IC
value of piperlongumine in the intracellular amastigote form of
was 0.4 µM, with a selectivity index of 25. The piperlongumine biomimetic derivatives, Ma and Mb, also showed leishmanicidal effects. We also carried out an
metabolic degradation study showing that Ma is the most stable piperlongumine derivative in rat liver microsome incubations. The results presented here indicate that piperlongumine is a potential leishmanicidal candidate and support the biomimetic approach for development of new antileishmanial derivatives.