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Furan derivatives impair proliferation and affect ultrastructural organization of Trypanosoma cruzi and Leishmania amazonensis
Chagas disease and leishmaniasis are neglected diseases caused by parasites of the Trypanosomatidae family and together they affect millions of people in the five continents. The treatment of Chagas disease is based on benznidazole, whereas for leishmaniasis few drugs are available, such as amphoter...
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Published in: | Experimental parasitology 2021-05, Vol.224, p.108100, Article 108100 |
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creator | Zuma, Aline Araujo Teixeira de Macedo-Silva, Sara Achari, Anushree Vinayagam, Jayaraman Bhattacharjee, Pinaki Chatterjee, Sourav Gupta, Vivek Kumar Cristina de Sousa Leite, Amanda Souza de Castro, Lucas Jaisankar, Parasuraman de Souza, Wanderley |
description | Chagas disease and leishmaniasis are neglected diseases caused by parasites of the Trypanosomatidae family and together they affect millions of people in the five continents. The treatment of Chagas disease is based on benznidazole, whereas for leishmaniasis few drugs are available, such as amphotericin B and miltefosine. In both cases, the current treatment is not entirely efficient due to toxicity or side effects. Encouraged by the need to discover valid targets and new treatment options, we evaluated 8 furan compounds against Trypanosoma cruzi and Leishmania amazonensis, considering their effects against proliferation, infection, and ultrastructure. Many of them were able to impair T. cruzi and L. amazonensis proliferation, as well as cause ultrastructural alterations, such as Golgi apparatus disorganization, autophagosome formation, and mitochondrial swelling. Taken together, the results obtained so far make these compounds eligible for further steps of chemotherapy study.
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•Furan derivatives are effective against pathogenic parasites proliferation.•Intracellular amastigote population decreased after treatment.•Furan derivatives led to unpacking of nuclear and mitochondrial DNA.•Loss of typical cell morphology was frequently observed. |
doi_str_mv | 10.1016/j.exppara.2021.108100 |
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[Display omitted]
•Furan derivatives are effective against pathogenic parasites proliferation.•Intracellular amastigote population decreased after treatment.•Furan derivatives led to unpacking of nuclear and mitochondrial DNA.•Loss of typical cell morphology was frequently observed.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1016/j.exppara.2021.108100</identifier><identifier>PMID: 33744229</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Cell Line ; Chagas Disease - drug therapy ; Chagas Disease - parasitology ; Chemotherapy ; Chromatography, Thin Layer ; Endemic Diseases ; Furan derivatives ; Furans - chemistry ; Furans - pharmacology ; Humans ; Inhibitory Concentration 50 ; Leishmania amazonensis ; Leishmania mexicana - drug effects ; Leishmania mexicana - growth & development ; Leishmania mexicana - ultrastructure ; Leishmaniasis, Cutaneous - drug therapy ; Leishmaniasis, Cutaneous - parasitology ; Macrophages ; Magnetic Resonance Spectroscopy ; Microscopy, Electron, Scanning ; Molecular Docking Simulation ; Neglected Diseases - drug therapy ; Neglected Diseases - parasitology ; Trypanosoma cruzi ; Trypanosoma cruzi - drug effects ; Trypanosoma cruzi - growth & development ; Trypanosoma cruzi - ultrastructure ; Ultrastructure</subject><ispartof>Experimental parasitology, 2021-05, Vol.224, p.108100, Article 108100</ispartof><rights>2021 Elsevier Inc.</rights><rights>Copyright © 2021 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-69b9b2139247781dd7f8be7a9c24cf0feaf6e6984962454a7ba19ff7873caa183</citedby><cites>FETCH-LOGICAL-c365t-69b9b2139247781dd7f8be7a9c24cf0feaf6e6984962454a7ba19ff7873caa183</cites><orcidid>0000-0002-6286-7908</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33744229$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zuma, Aline Araujo</creatorcontrib><creatorcontrib>Teixeira de Macedo-Silva, Sara</creatorcontrib><creatorcontrib>Achari, Anushree</creatorcontrib><creatorcontrib>Vinayagam, Jayaraman</creatorcontrib><creatorcontrib>Bhattacharjee, Pinaki</creatorcontrib><creatorcontrib>Chatterjee, Sourav</creatorcontrib><creatorcontrib>Gupta, Vivek Kumar</creatorcontrib><creatorcontrib>Cristina de Sousa Leite, Amanda</creatorcontrib><creatorcontrib>Souza de Castro, Lucas</creatorcontrib><creatorcontrib>Jaisankar, Parasuraman</creatorcontrib><creatorcontrib>de Souza, Wanderley</creatorcontrib><title>Furan derivatives impair proliferation and affect ultrastructural organization of Trypanosoma cruzi and Leishmania amazonensis</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>Chagas disease and leishmaniasis are neglected diseases caused by parasites of the Trypanosomatidae family and together they affect millions of people in the five continents. The treatment of Chagas disease is based on benznidazole, whereas for leishmaniasis few drugs are available, such as amphotericin B and miltefosine. In both cases, the current treatment is not entirely efficient due to toxicity or side effects. Encouraged by the need to discover valid targets and new treatment options, we evaluated 8 furan compounds against Trypanosoma cruzi and Leishmania amazonensis, considering their effects against proliferation, infection, and ultrastructure. Many of them were able to impair T. cruzi and L. amazonensis proliferation, as well as cause ultrastructural alterations, such as Golgi apparatus disorganization, autophagosome formation, and mitochondrial swelling. Taken together, the results obtained so far make these compounds eligible for further steps of chemotherapy study.
[Display omitted]
•Furan derivatives are effective against pathogenic parasites proliferation.•Intracellular amastigote population decreased after treatment.•Furan derivatives led to unpacking of nuclear and mitochondrial DNA.•Loss of typical cell morphology was frequently observed.</description><subject>Cell Line</subject><subject>Chagas Disease - drug therapy</subject><subject>Chagas Disease - parasitology</subject><subject>Chemotherapy</subject><subject>Chromatography, Thin Layer</subject><subject>Endemic Diseases</subject><subject>Furan derivatives</subject><subject>Furans - chemistry</subject><subject>Furans - pharmacology</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Leishmania amazonensis</subject><subject>Leishmania mexicana - drug effects</subject><subject>Leishmania mexicana - growth & development</subject><subject>Leishmania mexicana - ultrastructure</subject><subject>Leishmaniasis, Cutaneous - drug therapy</subject><subject>Leishmaniasis, Cutaneous - parasitology</subject><subject>Macrophages</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Microscopy, Electron, Scanning</subject><subject>Molecular Docking Simulation</subject><subject>Neglected Diseases - drug therapy</subject><subject>Neglected Diseases - parasitology</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosoma cruzi - drug effects</subject><subject>Trypanosoma cruzi - growth & development</subject><subject>Trypanosoma cruzi - ultrastructure</subject><subject>Ultrastructure</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkMFO3DAQQK2qCLbAJ7TyD2RrO94kPlUIFai0Ehc4WxNnTL3axNE4WZU98O2YBnrtydLovRnrMfZVirUUsvq-W-OfcQSCtRJK5lkjhfjEVlIYUSitzWe2EkLqQjdGn7EvKe2EyJDSp-ysLGutlTIr9nIzEwy8QwoHmMIBEw_9CIH4SHEfPFKexoHD0HHwHt3E5_1EkCaa3ZTdPY_0BEM4Llz0_IGeRxhiij1wR_Mx_JW3GNLvPoPAoYdjHHBIIV2wEw_7hJfv7zl7vPn5cH1XbO9vf11fbQtXVpupqExrWiVLo3RdN7Lrat-0WINxSjsvPIKvsDKNNpXSGw11C9J4Xzd16QBkU56zzbLXUUyJ0NuRQg_0bKWwbz3tzr73tG897dIze98Wb5zbHrt_1kfADPxYAMy_PwQkm1zAwWEXKMeyXQz_OfEK6OCNpQ</recordid><startdate>202105</startdate><enddate>202105</enddate><creator>Zuma, Aline Araujo</creator><creator>Teixeira de Macedo-Silva, Sara</creator><creator>Achari, Anushree</creator><creator>Vinayagam, Jayaraman</creator><creator>Bhattacharjee, Pinaki</creator><creator>Chatterjee, Sourav</creator><creator>Gupta, Vivek Kumar</creator><creator>Cristina de Sousa Leite, Amanda</creator><creator>Souza de Castro, Lucas</creator><creator>Jaisankar, Parasuraman</creator><creator>de Souza, Wanderley</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-6286-7908</orcidid></search><sort><creationdate>202105</creationdate><title>Furan derivatives impair proliferation and affect ultrastructural organization of Trypanosoma cruzi and Leishmania amazonensis</title><author>Zuma, Aline Araujo ; Teixeira de Macedo-Silva, Sara ; Achari, Anushree ; Vinayagam, Jayaraman ; Bhattacharjee, Pinaki ; Chatterjee, Sourav ; Gupta, Vivek Kumar ; Cristina de Sousa Leite, Amanda ; Souza de Castro, Lucas ; Jaisankar, Parasuraman ; de Souza, Wanderley</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-69b9b2139247781dd7f8be7a9c24cf0feaf6e6984962454a7ba19ff7873caa183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cell Line</topic><topic>Chagas Disease - drug therapy</topic><topic>Chagas Disease - parasitology</topic><topic>Chemotherapy</topic><topic>Chromatography, Thin Layer</topic><topic>Endemic Diseases</topic><topic>Furan derivatives</topic><topic>Furans - chemistry</topic><topic>Furans - pharmacology</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Leishmania amazonensis</topic><topic>Leishmania mexicana - drug effects</topic><topic>Leishmania mexicana - growth & development</topic><topic>Leishmania mexicana - ultrastructure</topic><topic>Leishmaniasis, Cutaneous - drug therapy</topic><topic>Leishmaniasis, Cutaneous - parasitology</topic><topic>Macrophages</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Microscopy, Electron, Scanning</topic><topic>Molecular Docking Simulation</topic><topic>Neglected Diseases - drug therapy</topic><topic>Neglected Diseases - parasitology</topic><topic>Trypanosoma cruzi</topic><topic>Trypanosoma cruzi - drug effects</topic><topic>Trypanosoma cruzi - growth & development</topic><topic>Trypanosoma cruzi - ultrastructure</topic><topic>Ultrastructure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zuma, Aline Araujo</creatorcontrib><creatorcontrib>Teixeira de Macedo-Silva, Sara</creatorcontrib><creatorcontrib>Achari, Anushree</creatorcontrib><creatorcontrib>Vinayagam, Jayaraman</creatorcontrib><creatorcontrib>Bhattacharjee, Pinaki</creatorcontrib><creatorcontrib>Chatterjee, Sourav</creatorcontrib><creatorcontrib>Gupta, Vivek Kumar</creatorcontrib><creatorcontrib>Cristina de Sousa Leite, Amanda</creatorcontrib><creatorcontrib>Souza de Castro, Lucas</creatorcontrib><creatorcontrib>Jaisankar, Parasuraman</creatorcontrib><creatorcontrib>de Souza, Wanderley</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zuma, Aline Araujo</au><au>Teixeira de Macedo-Silva, Sara</au><au>Achari, Anushree</au><au>Vinayagam, Jayaraman</au><au>Bhattacharjee, Pinaki</au><au>Chatterjee, Sourav</au><au>Gupta, Vivek Kumar</au><au>Cristina de Sousa Leite, Amanda</au><au>Souza de Castro, Lucas</au><au>Jaisankar, Parasuraman</au><au>de Souza, Wanderley</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Furan derivatives impair proliferation and affect ultrastructural organization of Trypanosoma cruzi and Leishmania amazonensis</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>2021-05</date><risdate>2021</risdate><volume>224</volume><spage>108100</spage><pages>108100-</pages><artnum>108100</artnum><issn>0014-4894</issn><eissn>1090-2449</eissn><abstract>Chagas disease and leishmaniasis are neglected diseases caused by parasites of the Trypanosomatidae family and together they affect millions of people in the five continents. The treatment of Chagas disease is based on benznidazole, whereas for leishmaniasis few drugs are available, such as amphotericin B and miltefosine. In both cases, the current treatment is not entirely efficient due to toxicity or side effects. Encouraged by the need to discover valid targets and new treatment options, we evaluated 8 furan compounds against Trypanosoma cruzi and Leishmania amazonensis, considering their effects against proliferation, infection, and ultrastructure. Many of them were able to impair T. cruzi and L. amazonensis proliferation, as well as cause ultrastructural alterations, such as Golgi apparatus disorganization, autophagosome formation, and mitochondrial swelling. Taken together, the results obtained so far make these compounds eligible for further steps of chemotherapy study.
[Display omitted]
•Furan derivatives are effective against pathogenic parasites proliferation.•Intracellular amastigote population decreased after treatment.•Furan derivatives led to unpacking of nuclear and mitochondrial DNA.•Loss of typical cell morphology was frequently observed.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33744229</pmid><doi>10.1016/j.exppara.2021.108100</doi><orcidid>https://orcid.org/0000-0002-6286-7908</orcidid></addata></record> |
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subjects | Cell Line Chagas Disease - drug therapy Chagas Disease - parasitology Chemotherapy Chromatography, Thin Layer Endemic Diseases Furan derivatives Furans - chemistry Furans - pharmacology Humans Inhibitory Concentration 50 Leishmania amazonensis Leishmania mexicana - drug effects Leishmania mexicana - growth & development Leishmania mexicana - ultrastructure Leishmaniasis, Cutaneous - drug therapy Leishmaniasis, Cutaneous - parasitology Macrophages Magnetic Resonance Spectroscopy Microscopy, Electron, Scanning Molecular Docking Simulation Neglected Diseases - drug therapy Neglected Diseases - parasitology Trypanosoma cruzi Trypanosoma cruzi - drug effects Trypanosoma cruzi - growth & development Trypanosoma cruzi - ultrastructure Ultrastructure |
title | Furan derivatives impair proliferation and affect ultrastructural organization of Trypanosoma cruzi and Leishmania amazonensis |
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