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Abstract Title:

Leishmanicidal effects of piperine, its derivatives, and analogues on Leishmania amazonensis.

Abstract Source:

Phytochemistry. 2011 Dec ;72(17):2155-64. Epub 2011 Aug 30. PMID: 21885074

Abstract Author(s):

C Ferreira, D C Soares, C B Barreto-Junior, M T Nascimento, L Freire-de-Lima, J C Delorenzi, M E F Lima, G C Atella, E Folly, T M U Carvalho, E M Saraiva, L H Pinto-da-Silva

Article Affiliation:

C Ferreira

Abstract:

Leishmaniasis is a tropical disease caused by protozoan parasites of the genus Leishmania which affects 12 million people worldwide. The discovery of drugs for the treatment of leishmaniasis is a pressing concern in global health programs. The aim of this study aim was to evaluate the leishmanicidal effect of piperine and its derivatives/analogues on Leishmania amazonensis. Our results showed that piperine and phenylamide are active against promastigotes and amastigotes in infected macrophages. Both drugs induced mitochondrial swelling, loose kinetoplast DNA, and led to loss of mitochondrial membrane potential. The promastigote cell cycle was also affected with an increase in the G1 phase cells and a decrease in the S-phase cells, respectively, after piperine and phenylamide treatment. Lipid analysis of promastigotes showed that piperine reduced triglyceride, diacylglycerol, and monoacylglycerol contents, whereas phenylamide only reduced diacylglycerol levels. Both drugs were deemed non toxic to macrophages at 50μM as assessed by XTT (sodium 2,3,-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium inner salt), Trypan blue exclusion, and phagocytosis assays, whereas low toxicity was noted at concentrations higher than 150 μM. None of the drugs induced nitric oxide (NO) production. By contrast, piperine reduced NO production in activated macrophages. The isobologram analysis showed that piperine and phenylamide acted synergistically on the parasites suggesting that they affect different target mechanisms. These results indicate that piperine and its phenylamide analogue arecandidates for development of drugs for cutaneous leishmaniasis treatment.

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Sayer Ji
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