Details
| Original language | English |
|---|---|
| Pages (from-to) | 9083-9090 |
| Number of pages | 8 |
| Journal | Chemistry - A European Journal |
| Volume | 18 |
| Issue number | 29 |
| Publication status | Published - 13 Jun 2012 |
Abstract
The total synthesis of 16 new ion channel inhibitors derived from noricumazole A, a secondary metabolite from the myxobacterium Sorangium cellulosum, is reported. Particular focus of library design is put on stereochemical permutations in the central region (C9 and C11), the oxazole moiety and the side chain at C4 of the isochromanone moiety. Noricumazole A and all new noricumazole derivatives were tested in an assay system with inhibitory effect on the hepatitis C virus (HCV) life cycle. Most of them are moderate to strong HCV inhibitors (350 nM-6 nM) but also exert pronounced cytotoxicity. In contrast, the thiazole analogue of noricumazole A is a strong HCV inhibitor with only moderate cytotoxic property. It may become a lead structure with a good therapeutic index (CC 50/IC 50) of greater than 10.
Keywords
- compound library, Hepatitis C virus, iron catalysis, natural products, total synthesis
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
Sustainable Development Goals
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In: Chemistry - A European Journal, Vol. 18, No. 29, 13.06.2012, p. 9083-9090.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Total synthesis of a noricumazole A library and evaluation of HCV inhibition
AU - Barbier, Jenny
AU - Wegner, Jens
AU - Benson, Stefan
AU - Gentzsch, Juliane
AU - Pietschmann, Thomas
AU - Kirschning, Andreas
PY - 2012/6/13
Y1 - 2012/6/13
N2 - The total synthesis of 16 new ion channel inhibitors derived from noricumazole A, a secondary metabolite from the myxobacterium Sorangium cellulosum, is reported. Particular focus of library design is put on stereochemical permutations in the central region (C9 and C11), the oxazole moiety and the side chain at C4 of the isochromanone moiety. Noricumazole A and all new noricumazole derivatives were tested in an assay system with inhibitory effect on the hepatitis C virus (HCV) life cycle. Most of them are moderate to strong HCV inhibitors (350 nM-6 nM) but also exert pronounced cytotoxicity. In contrast, the thiazole analogue of noricumazole A is a strong HCV inhibitor with only moderate cytotoxic property. It may become a lead structure with a good therapeutic index (CC 50/IC 50) of greater than 10.
AB - The total synthesis of 16 new ion channel inhibitors derived from noricumazole A, a secondary metabolite from the myxobacterium Sorangium cellulosum, is reported. Particular focus of library design is put on stereochemical permutations in the central region (C9 and C11), the oxazole moiety and the side chain at C4 of the isochromanone moiety. Noricumazole A and all new noricumazole derivatives were tested in an assay system with inhibitory effect on the hepatitis C virus (HCV) life cycle. Most of them are moderate to strong HCV inhibitors (350 nM-6 nM) but also exert pronounced cytotoxicity. In contrast, the thiazole analogue of noricumazole A is a strong HCV inhibitor with only moderate cytotoxic property. It may become a lead structure with a good therapeutic index (CC 50/IC 50) of greater than 10.
KW - compound library
KW - Hepatitis C virus
KW - iron catalysis
KW - natural products
KW - total synthesis
UR - http://www.scopus.com/inward/record.url?scp=84863707474&partnerID=8YFLogxK
U2 - 10.1002/chem.201104042
DO - 10.1002/chem.201104042
M3 - Article
C2 - 22696300
AN - SCOPUS:84863707474
VL - 18
SP - 9083
EP - 9090
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 29
ER -