Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems
Schistosomiasis is one of the 17 neglected tropical diseases prioritized by the World Health Organization. It affects hundreds of millions of people in developing countries in the poorest tropical and subtropical regions of the world. Today, essentially a single drug, praziquantel (PZQ), is availabl...
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Public Library of Science
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982595/ |
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pubmed-49825952016-08-29 Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems Guidi, Alessandra Lalli, Cristiana Perlas, Emerald Bolasco, Giulia Nibbio, Martina Monteagudo, Edith Bresciani, Alberto Ruberti, Giovina Research Article Schistosomiasis is one of the 17 neglected tropical diseases prioritized by the World Health Organization. It affects hundreds of millions of people in developing countries in the poorest tropical and subtropical regions of the world. Today, essentially a single drug, praziquantel (PZQ), is available to treat this parasitic disease. PZQ incomplete efficacy across all stages of the Schistosoma mansoni life cycle in the definitive host and the potential risk of drug resistance prompted us to search for novel schistosomicidal molecules. We screened a compound collection library using the larval stage of the parasite and discovered novel anti-schistosomal properties of perhexiline maleate (PHX). Overall, our study demonstrated that the anti-anginal drug PHX, still used in some countries, is active in vitro against parasite life stages poorly sensitive to PZQ. In addition, we showed that PHX impairs egg production in mature worm couples in vitro and damages the female and male reproductive systems and the male worm tegument. PHX could therefore represent a promising starting point for novel schistosomicidal drug discovery programmes. Public Library of Science 2016-08-12 /pmc/articles/PMC4982595/ /pubmed/27518281 http://dx.doi.org/10.1371/journal.pntd.0004928 Text en © 2016 Guidi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Guidi, Alessandra Lalli, Cristiana Perlas, Emerald Bolasco, Giulia Nibbio, Martina Monteagudo, Edith Bresciani, Alberto Ruberti, Giovina |
| spellingShingle |
Guidi, Alessandra Lalli, Cristiana Perlas, Emerald Bolasco, Giulia Nibbio, Martina Monteagudo, Edith Bresciani, Alberto Ruberti, Giovina Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems |
| author_facet |
Guidi, Alessandra Lalli, Cristiana Perlas, Emerald Bolasco, Giulia Nibbio, Martina Monteagudo, Edith Bresciani, Alberto Ruberti, Giovina |
| author_sort |
Guidi, Alessandra |
| title |
Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems |
| title_short |
Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems |
| title_full |
Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems |
| title_fullStr |
Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems |
| title_full_unstemmed |
Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems |
| title_sort |
discovery and characterization of novel anti-schistosomal properties of the anti-anginal drug, perhexiline and its impact on schistosoma mansoni male and female reproductive systems |
| description |
Schistosomiasis is one of the 17 neglected tropical diseases prioritized by the World Health Organization. It affects hundreds of millions of people in developing countries in the poorest tropical and subtropical regions of the world. Today, essentially a single drug, praziquantel (PZQ), is available to treat this parasitic disease. PZQ incomplete efficacy across all stages of the Schistosoma mansoni life cycle in the definitive host and the potential risk of drug resistance prompted us to search for novel schistosomicidal molecules. We screened a compound collection library using the larval stage of the parasite and discovered novel anti-schistosomal properties of perhexiline maleate (PHX). Overall, our study demonstrated that the anti-anginal drug PHX, still used in some countries, is active in vitro against parasite life stages poorly sensitive to PZQ. In addition, we showed that PHX impairs egg production in mature worm couples in vitro and damages the female and male reproductive systems and the male worm tegument. PHX could therefore represent a promising starting point for novel schistosomicidal drug discovery programmes. |
| publisher |
Public Library of Science |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982595/ |
| _version_ |
1613626672413671424 |