کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1355681 981055 2013 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and characterization of a small analogue of the anticancer natural product leinamycin
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and characterization of a small analogue of the anticancer natural product leinamycin
چکیده انگلیسی

Leinamycin (1) is a Streptomyces-derived natural product that displays nanomolar IC50 values against human cancer cell lines. In the work described here, we report the synthesis and characterization of a small leinamycin analogue 19 that closely resembles the ‘upper-right quadrant’ of the natural product, consisting of an alicyclic 1,2-dithiolan-3-one 1-oxide heterocycle connected to an alkene by a two-carbon linker. The results indicate that this small analogue contains the core set of functional groups required to enable thiol-triggered generation of both redox active polysulfides and an episulfonium ion intermediate via the complex reaction cascade first seen in the natural product leinamycin. The small leinamycin analogue 19 caused thiol-triggered oxidative DNA strand cleavage in a manner similar to the natural product, but did not alkyate duplex DNA effectively. This highlights the central role of the 18-membered macrocycle of leinamycin in driving efficient DNA alkylation by the natural product.

A small analogue of the natural product leinamycin was prepared containing the core set of functional groups required to enable thiol-triggered generation of both redox active polysulfides and an episulfonium ion intermediate via the complex reaction cascade first seen in the natural product leinamycin.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 1, 1 January 2013, Pages 235–241
نویسندگان
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