کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5674308 1408224 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel synthetic compounds with endoperoxide structure damage juvenile stage of Schistosoma mansoni by targeting lysosome-like organelles
ترجمه فارسی عنوان
ترکیبات مصنوعی رمان با ساختار اندپورکسید باعث آسیب رسیدن به مرحله جوانه زدن شیستوزومای مانسونی با هدف قرار دادن اندام های لیزوزوم مانند
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی انگل شناسی
چکیده انگلیسی


- N-251 exhibited high schistosmicidal activity in vitro.
- N-251 accumulated in acidic organelles.
- N-251 damaged and disrupted lysosomal organelles.

The new synthetic compound 1,2,6,7-tetraoxaspiro[7.11]nonadecan (N-89), a novel anti-malaria drug candidate, is also a promising drug candidate against schistosomiasis with killing effects against juvenile stage of S. mansoni. In order to investigate how N-89 kills schistosomes, we used a derivative of N-89, 6-(1,2,6,7-tetraoxaspiro[7.11] nonadec-4-yl)hexan-1-ol (N-251), which enables us to conjugate with fluorescent reagents. Firstly, N-251 showed strong killing effects to larvae of S. mansoni in vitro. Ultrastructural analysis showed the disruptions of the lysosome-like organelles or the acetabular glands, followed by cytoplasmic lysis inside the worm body in N-251-treated group under electron microscopy. For rhodamine-conjugated N-251 and organelle markers, we observed that N-251 accumulated in acidic organelle. In addition, LysoTracker signals in these acidic organelles disappeared in N-251-treated group over time. Finally, we observed that the activity of cathepsin B, a lysosome-specific enzyme, was also decreased together with alternation of acidic organelle marker signal by N-251-treated group. These results suggested that our synthesized compounds induced the dysfunction or the disruption of acidic lysosome-like organelles and finally led to worm death.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Parasitology International - Volume 66, Issue 1, February 2017, Pages 917-924
نویسندگان
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