In vivo studies of the effect of PPQ-6, a quinoline-based agent against Schistosoma mansoni in mice
Schistosomiasis is still a public health problem. Praziquantel is the only drug available for treatment of all forms of human schistosomiasis. Although praziquantel is an effective drug against all species of human schistosomes, concerns about resistance have been raised, especially in endemic areas...
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Veröffentlicht in: | Experimental parasitology 2020-08, Vol.215, p.107933-107933, Article 107933 |
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creator | Taman, Amira Alhusseiny, Samar M. El-Zayady, Wafaa M. Elblihy, Ayat A. Mansour, Basem Massoud, Mohammed Youssef, Mona Younis Saleh, Nora E. |
description | Schistosomiasis is still a public health problem. Praziquantel is the only drug available for treatment of all forms of human schistosomiasis. Although praziquantel is an effective drug against all species of human schistosomes, concerns about resistance have been raised, especially in endemic areas. A hybrid compound containing several pharmacophore within a single molecule is a promising strategy. Here, we described the anti-schistosomal effect of 4-(2-Chloroquinolin-3-yl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (PPQ-6), a hybrid drug based on quinoline and pyridine. PPQ-6 was given as two regimens (20 or 40 mg/kg). In both regimens, PPQ-6 significantly reduced liver and spleen indices, nitric oxide production, tissue egg load, hepatic granuloma size and count, immature eggs and total worm burden especially females. Our findings suggested that PPQ-6 is a promising anti-schistosomal agent; however more research is needed to elucidate its mechanism of action and report its activity on juvenile schistosomes and other species of human schistosomes.
[Display omitted]
•PPQ-6 is a new hybrid compound based on quinoline and pyridine.•PPQ-6 showed promising antischistosomal effect in experimentally infected mice.•The antischistosomal effect was dose-dependent.•Morphological examination of PPQ-6 treated worms showed Hz reduction.•Female worms seemed more sensitive to PPQ-6 than male worms. |
doi_str_mv | 10.1016/j.exppara.2020.107933 |
format | Article |
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[Display omitted]
•PPQ-6 is a new hybrid compound based on quinoline and pyridine.•PPQ-6 showed promising antischistosomal effect in experimentally infected mice.•The antischistosomal effect was dose-dependent.•Morphological examination of PPQ-6 treated worms showed Hz reduction.•Female worms seemed more sensitive to PPQ-6 than male worms.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1016/j.exppara.2020.107933</identifier><language>eng</language><publisher>Elsevier Inc</publisher><subject>Granuloma ; Hemozoin ; PPQ-6 ; Quinoline ; Schistosoma mansoni</subject><ispartof>Experimental parasitology, 2020-08, Vol.215, p.107933-107933, Article 107933</ispartof><rights>2020 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c342t-99313ce4a8b308c789165d96f44beba5e1985827b89f5e3c27140c18523b4b33</citedby><cites>FETCH-LOGICAL-c342t-99313ce4a8b308c789165d96f44beba5e1985827b89f5e3c27140c18523b4b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.exppara.2020.107933$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids></links><search><creatorcontrib>Taman, Amira</creatorcontrib><creatorcontrib>Alhusseiny, Samar M.</creatorcontrib><creatorcontrib>El-Zayady, Wafaa M.</creatorcontrib><creatorcontrib>Elblihy, Ayat A.</creatorcontrib><creatorcontrib>Mansour, Basem</creatorcontrib><creatorcontrib>Massoud, Mohammed</creatorcontrib><creatorcontrib>Youssef, Mona Younis</creatorcontrib><creatorcontrib>Saleh, Nora E.</creatorcontrib><title>In vivo studies of the effect of PPQ-6, a quinoline-based agent against Schistosoma mansoni in mice</title><title>Experimental parasitology</title><description>Schistosomiasis is still a public health problem. Praziquantel is the only drug available for treatment of all forms of human schistosomiasis. Although praziquantel is an effective drug against all species of human schistosomes, concerns about resistance have been raised, especially in endemic areas. A hybrid compound containing several pharmacophore within a single molecule is a promising strategy. Here, we described the anti-schistosomal effect of 4-(2-Chloroquinolin-3-yl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (PPQ-6), a hybrid drug based on quinoline and pyridine. PPQ-6 was given as two regimens (20 or 40 mg/kg). In both regimens, PPQ-6 significantly reduced liver and spleen indices, nitric oxide production, tissue egg load, hepatic granuloma size and count, immature eggs and total worm burden especially females. Our findings suggested that PPQ-6 is a promising anti-schistosomal agent; however more research is needed to elucidate its mechanism of action and report its activity on juvenile schistosomes and other species of human schistosomes.
[Display omitted]
•PPQ-6 is a new hybrid compound based on quinoline and pyridine.•PPQ-6 showed promising antischistosomal effect in experimentally infected mice.•The antischistosomal effect was dose-dependent.•Morphological examination of PPQ-6 treated worms showed Hz reduction.•Female worms seemed more sensitive to PPQ-6 than male worms.</description><subject>Granuloma</subject><subject>Hemozoin</subject><subject>PPQ-6</subject><subject>Quinoline</subject><subject>Schistosoma mansoni</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkN1LwzAUxYMoOKd_gpBHH-zMV9vkSUT8GAycuPeQprcuo026ph3639vRvftyL_dyzoHzQ-iWkgUlNHvYLeCnbU1nFoyw4y9XnJ-hGSWKJEwIdY5mhFCRCKnEJbqKcUcIkZSJGbJLjw_uEHDsh9JBxKHC_RYwVBXY_nit159Jdo8N3g_Oh9p5SAoTocTmG3w_TuN87PGX3brYhxgagxvjY_AOO48bZ-EaXVSmjnBz2nO0eX3ZPL8nq4-35fPTKrFcsD5RilNuQRhZcCJtLhXN0lJllRAFFCYFqmQqWV5IVaXALcupIJbKlPFCFJzP0d0U23ZhP0DsdeOihbo2HsIQNROUMaIyno3SdJLaLsTYQaXbzjWm-9WU6CNTvdMnpvrIVE9MR9_j5IOxxsFBp6N14C2Urhtx6TK4fxL-AGfWgTs</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Taman, Amira</creator><creator>Alhusseiny, Samar M.</creator><creator>El-Zayady, Wafaa M.</creator><creator>Elblihy, Ayat A.</creator><creator>Mansour, Basem</creator><creator>Massoud, Mohammed</creator><creator>Youssef, Mona Younis</creator><creator>Saleh, Nora E.</creator><general>Elsevier Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202008</creationdate><title>In vivo studies of the effect of PPQ-6, a quinoline-based agent against Schistosoma mansoni in mice</title><author>Taman, Amira ; Alhusseiny, Samar M. ; El-Zayady, Wafaa M. ; Elblihy, Ayat A. ; Mansour, Basem ; Massoud, Mohammed ; Youssef, Mona Younis ; Saleh, Nora E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c342t-99313ce4a8b308c789165d96f44beba5e1985827b89f5e3c27140c18523b4b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Granuloma</topic><topic>Hemozoin</topic><topic>PPQ-6</topic><topic>Quinoline</topic><topic>Schistosoma mansoni</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taman, Amira</creatorcontrib><creatorcontrib>Alhusseiny, Samar M.</creatorcontrib><creatorcontrib>El-Zayady, Wafaa M.</creatorcontrib><creatorcontrib>Elblihy, Ayat A.</creatorcontrib><creatorcontrib>Mansour, Basem</creatorcontrib><creatorcontrib>Massoud, Mohammed</creatorcontrib><creatorcontrib>Youssef, Mona Younis</creatorcontrib><creatorcontrib>Saleh, Nora E.</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taman, Amira</au><au>Alhusseiny, Samar M.</au><au>El-Zayady, Wafaa M.</au><au>Elblihy, Ayat A.</au><au>Mansour, Basem</au><au>Massoud, Mohammed</au><au>Youssef, Mona Younis</au><au>Saleh, Nora E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo studies of the effect of PPQ-6, a quinoline-based agent against Schistosoma mansoni in mice</atitle><jtitle>Experimental parasitology</jtitle><date>2020-08</date><risdate>2020</risdate><volume>215</volume><spage>107933</spage><epage>107933</epage><pages>107933-107933</pages><artnum>107933</artnum><issn>0014-4894</issn><eissn>1090-2449</eissn><abstract>Schistosomiasis is still a public health problem. Praziquantel is the only drug available for treatment of all forms of human schistosomiasis. Although praziquantel is an effective drug against all species of human schistosomes, concerns about resistance have been raised, especially in endemic areas. A hybrid compound containing several pharmacophore within a single molecule is a promising strategy. Here, we described the anti-schistosomal effect of 4-(2-Chloroquinolin-3-yl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (PPQ-6), a hybrid drug based on quinoline and pyridine. PPQ-6 was given as two regimens (20 or 40 mg/kg). In both regimens, PPQ-6 significantly reduced liver and spleen indices, nitric oxide production, tissue egg load, hepatic granuloma size and count, immature eggs and total worm burden especially females. Our findings suggested that PPQ-6 is a promising anti-schistosomal agent; however more research is needed to elucidate its mechanism of action and report its activity on juvenile schistosomes and other species of human schistosomes.
[Display omitted]
•PPQ-6 is a new hybrid compound based on quinoline and pyridine.•PPQ-6 showed promising antischistosomal effect in experimentally infected mice.•The antischistosomal effect was dose-dependent.•Morphological examination of PPQ-6 treated worms showed Hz reduction.•Female worms seemed more sensitive to PPQ-6 than male worms.</abstract><pub>Elsevier Inc</pub><doi>10.1016/j.exppara.2020.107933</doi><tpages>1</tpages></addata></record> |
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subjects | Granuloma Hemozoin PPQ-6 Quinoline Schistosoma mansoni |
title | In vivo studies of the effect of PPQ-6, a quinoline-based agent against Schistosoma mansoni in mice |
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