Tiacumicin Congeners with Improved Antibacterial Activity from a Halogenase-Inactivated Mutant
| Autor: | Xiaohui Pu, Changsheng Zhang, Wenjun Zhang, Haibo Zhang, Tian Xiaoxing, Qingbo Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Hydrolases
Stereochemistry Mutant Pharmaceutical Science Microbial Sensitivity Tests 010402 general chemistry Dactylosporangium aurantiacum 01 natural sciences Analytical Chemistry Drug Discovery medicine Fidaxomicin Pharmacology 010405 organic chemistry Chemistry Organic Chemistry Micromonosporaceae Tiacumicin B Clostridium difficile infections Anti-Bacterial Agents Biosynthetic Pathways 0104 chemical sciences Aminoglycosides Congener Complementary and alternative medicine Molecular Medicine Antibacterial activity medicine.drug |
| Zdroj: | Journal of Natural Products. 81:1219-1224 |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/acs.jnatprod.7b00990 |
| Popis: | Tiacumicin B (1, also known as fidaxomicin or difimicin) is a marketed drug for the treatment of Clostridium difficile infections. The biosynthetic pathway of 1 has been studied in Dactylosporangium aurantiacum subsp. hamdenensis NRRL 18085 and has enabled the identification of TiaM as a tailoring dihalogenase. Herein we report the isolation, structure elucidation, and bioactivity evaluation of 14 tiacumicin congeners (including 11 new ones) from the tiaM-inactivated mutant. A new tiacumicin congener, 3, with a propyl group at C-7‴ of the aromatic ring was found to exhibit improved antibacterial activity. |
| Databáze: | OpenAIRE |
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