کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9769222 1501244 2005 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and antimalarial activity of E-2-quinolinylbenzocycloalcanones
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and antimalarial activity of E-2-quinolinylbenzocycloalcanones
چکیده انگلیسی
A series of E-2-quinolinylbenzocycloalcanones 5-21 were prepared and evaluated for their activity to inhibit β-hematin formation and the hydrolysis of hemoglobin in vitro. Positive compounds for both assays were also tested for their efficacy in rodent Plasmodium berghei. Compounds 6, 16, 19, and 20, were the most promising. Inhibition of β-hematin formation was minimal when a hydrogen or methoxy groups were present on the position 8 of the quinoline and position 4′ of the indanone ring as it appeared for compounds 5, 7-15, 17, 18, and 21, and greatest with compounds (52%) and (90%) with a substitution of methoxy on position 6 and 7 or methyl on position 8 of the quinoline nucleus and methoxy or methyl groups on position 4′ of the indanone. The most active compound to emerge from this study is 2-chloro-8-methyl-3-[(4′-methoxy-1′-indanoyl)-2′-methyliden]-quinoline 20 effective as antimalarial that target β-hematin formation and the inhibition of the hydrolysis of hemoglobin in vitro together with a good survival in a murine malaria model, which should help delay the rapid onset of resistance to drugs acting at only a single site. Results with these assays suggest that quinolinylbenzocycloalcanones exert their antimalarial activity via multiple mechanisms.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 40, Issue 9, September 2005, Pages 875-881
نویسندگان
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