Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some Natural Sesquiterpene Lactones
Leishmaniases are neglected infectious diseases caused by parasites of the ‘protozoan’ genus Leishmania. Depending on the parasite species, different clinical forms are known as cutaneous, muco-cutaneous, and the visceral leishmaniasis (VL). VL is particularly fatal and the therapy presents limitati...
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| Format: | Article |
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MDPI AG
2017-04-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/22/5/685 |
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| author | Imke F. Wulsten Thais A. Costa-Silva Juliana T. Mesquita Marta L. Lima Mariana K. Galuppo Noemi N. Taniwaki Samanta E. T. Borborema Fernando B. Da Costa Thomas J. Schmidt Andre G. Tempone |
| author_facet | Imke F. Wulsten Thais A. Costa-Silva Juliana T. Mesquita Marta L. Lima Mariana K. Galuppo Noemi N. Taniwaki Samanta E. T. Borborema Fernando B. Da Costa Thomas J. Schmidt Andre G. Tempone |
| author_sort | Imke F. Wulsten |
| collection | DOAJ |
| description | Leishmaniases are neglected infectious diseases caused by parasites of the ‘protozoan’ genus Leishmania. Depending on the parasite species, different clinical forms are known as cutaneous, muco-cutaneous, and the visceral leishmaniasis (VL). VL is particularly fatal and the therapy presents limitations. In the search for new anti-leishmanial hit compounds, seven natural sesquiterpene lactones were evaluated against promastigotes and intracellular amastigotes of Leishmania (Leishmania) infantum, a pathogen causing VL. The pseudoguaianolides mexicanin I and helenalin acetate demonstrated the highest selectivity and potency against intracellular amastigotes. In addition, promastigotes treated with helenalin acetate were subject to an ultrastructural and biochemical investigation. The lethal action of the compound was investigated by fluorescence-activated cell sorting and related techniques to detect alterations in reactive oxygen species (ROS) content, plasma membrane permeability, and mitochondrial membrane potential. Helenalin acetate significantly reduced the mitochondrial membrane potential and the mitochondrial structural damage was also confirmed by transmission electron microscopy, displaying an intense organelle swelling. No alteration of plasma membrane permeability or ROS content could be detected. Additionally, helenalin acetate significantly increased the production of nitric oxide in peritoneal macrophages, probably potentiating the activity against the intracellular amastigotes. Helenalin acetate could hence be a useful anti-leishmanial scaffold for further optimization studies. |
| first_indexed | 2024-04-14T08:29:17Z |
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| id | doaj.art-b7a295e566b348debd0be2f472a12326 |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-14T08:29:17Z |
| publishDate | 2017-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b7a295e566b348debd0be2f472a123262022-12-22T02:03:57ZengMDPI AGMolecules1420-30492017-04-0122568510.3390/molecules22050685molecules22050685Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some Natural Sesquiterpene LactonesImke F. Wulsten0Thais A. Costa-Silva1Juliana T. Mesquita2Marta L. Lima3Mariana K. Galuppo4Noemi N. Taniwaki5Samanta E. T. Borborema6Fernando B. Da Costa7Thomas J. Schmidt8Andre G. Tempone9Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, 14195 Berlin, GermanyCentre for Parasitology and Mycology, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, CEP 01246-900 São Paulo, SP, BrazilCentre for Parasitology and Mycology, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, CEP 01246-900 São Paulo, SP, BrazilCentre for Parasitology and Mycology, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, CEP 01246-900 São Paulo, SP, BrazilCentre for Parasitology and Mycology, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, CEP 01246-900 São Paulo, SP, BrazilCentre for Parasitology and Mycology, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, CEP 01246-900 São Paulo, SP, BrazilCentre for Parasitology and Mycology, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, CEP 01246-900 São Paulo, SP, BrazilAsterBioChem Research Team, Laboratory of Pharmacognosy, School of Pharmaceutical Sciences of Ribeirão Preto, USP, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, BrazilInstitute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus, Corrensstraße 48, 48149 Münster, GermanyCentre for Parasitology and Mycology, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, CEP 01246-900 São Paulo, SP, BrazilLeishmaniases are neglected infectious diseases caused by parasites of the ‘protozoan’ genus Leishmania. Depending on the parasite species, different clinical forms are known as cutaneous, muco-cutaneous, and the visceral leishmaniasis (VL). VL is particularly fatal and the therapy presents limitations. In the search for new anti-leishmanial hit compounds, seven natural sesquiterpene lactones were evaluated against promastigotes and intracellular amastigotes of Leishmania (Leishmania) infantum, a pathogen causing VL. The pseudoguaianolides mexicanin I and helenalin acetate demonstrated the highest selectivity and potency against intracellular amastigotes. In addition, promastigotes treated with helenalin acetate were subject to an ultrastructural and biochemical investigation. The lethal action of the compound was investigated by fluorescence-activated cell sorting and related techniques to detect alterations in reactive oxygen species (ROS) content, plasma membrane permeability, and mitochondrial membrane potential. Helenalin acetate significantly reduced the mitochondrial membrane potential and the mitochondrial structural damage was also confirmed by transmission electron microscopy, displaying an intense organelle swelling. No alteration of plasma membrane permeability or ROS content could be detected. Additionally, helenalin acetate significantly increased the production of nitric oxide in peritoneal macrophages, probably potentiating the activity against the intracellular amastigotes. Helenalin acetate could hence be a useful anti-leishmanial scaffold for further optimization studies.http://www.mdpi.com/1420-3049/22/5/685sesquiterpene lactonespseudoguaianolideshelenalin acetatemexicanin ILeishmania (L.) infantumdrugsnitric oxide |
| spellingShingle | Imke F. Wulsten Thais A. Costa-Silva Juliana T. Mesquita Marta L. Lima Mariana K. Galuppo Noemi N. Taniwaki Samanta E. T. Borborema Fernando B. Da Costa Thomas J. Schmidt Andre G. Tempone Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some Natural Sesquiterpene Lactones Molecules sesquiterpene lactones pseudoguaianolides helenalin acetate mexicanin I Leishmania (L.) infantum drugs nitric oxide |
| title | Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some Natural Sesquiterpene Lactones |
| title_full | Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some Natural Sesquiterpene Lactones |
| title_fullStr | Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some Natural Sesquiterpene Lactones |
| title_full_unstemmed | Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some Natural Sesquiterpene Lactones |
| title_short | Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some Natural Sesquiterpene Lactones |
| title_sort | investigation of the anti leishmania leishmania infantum activity of some natural sesquiterpene lactones |
| topic | sesquiterpene lactones pseudoguaianolides helenalin acetate mexicanin I Leishmania (L.) infantum drugs nitric oxide |
| url | http://www.mdpi.com/1420-3049/22/5/685 |
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