کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1357903 981304 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Endoperoxide polyketides from a Chinese Plakortis simplex: Further evidence of the impact of stereochemistry on antimalarial activity of simple 1,2-dioxanes
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Endoperoxide polyketides from a Chinese Plakortis simplex: Further evidence of the impact of stereochemistry on antimalarial activity of simple 1,2-dioxanes
چکیده انگلیسی

Chemical investigation of the organic extract obtained from the sponge Plakortis simplex collected in the South China Sea afforded five new polyketide endoperoxides (2 and 4–7), along with two known analogues (1 and 3). The stereostructures of these metabolites have been deduced on the basis of spectroscopic analysis and chemical conversion. The isolated endoperoxide derivatives have been tested for their in vitro antimalarial activity against Plasmodium falciparum strains, showing IC50 values in the low micromolar range. The structure–activity relationships were analyzed by means of a detailed computational investigation and rationalized in the light of the mechanism of action proposed for this class of simple antimalarials. The relative orientation of the atoms involved in the putative radical generation and transfer reaction was demonstrated to have a great impact on the antimalarial activity. The resulting 3D pharmacophoric model can be a useful guide to design simple and effective antimalarial lead compounds belonging to the class of 1,2-dioxanes.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 17, 1 September 2014, Pages 4572–4580
نویسندگان
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