The macrocycle of leinamycin imparts hydrolytic stability to the thiol-sensing 1,2-dithiolan-3-one 1-oxide unit of the natural product.
نویسندگان
چکیده
Reaction of cellular thiols with the 1,2-dithiolan-3-one 1-oxide moiety of leinamycin triggers the generation of DNA-damaging reactive intermediates. Studies with small, synthetic analogues of leinamycin reveal that the macrocyclic portion of the natural product imparts remarkable hydrolytic stability to the 1,2-dithiolan-3-one 1-oxide heterocycle without substantially compromising its thiol-sensing property.
منابع مشابه
1,2-Dithiolan-3-one 1-oxides: a class of thiol-activated DNA-cleaving agents that are structurally related to the natural product leinamycin.
Leinamycin is a recently discovered, thiol-dependent DNA-cleaving natural product. The mechanism of DNA cleavage by leinamycin is unknown. Inspired by this intriguing natural product, we have investigated the DNA-cleaving properties of three 1,2-dithiolan-3-one 1-oxides (1-3) that are structurally related to the suspected DNA-cleaving "core" of leinamycin. It was found that, similar to leinamyc...
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Reaction of thiols with the 1,2-dithiolan-3-one 1-oxide heterocycle found in leinamycin (1) results in the conversion of this antitumor antibiotic to a DNA-alkylating episulfonium ion (5). While the products formed in this reaction have been rationalized by a mechanism involving initial attack of thiol on the central sulfenyl sulfur (S2') of the 1,2-dithiolan-3-one 1-oxide ring, the carbonyl ca...
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ورودعنوان ژورنال:
- Bioorganic & medicinal chemistry letters
دوره 22 11 شماره
صفحات -
تاریخ انتشار 2012