Synthesis and Antimicrobial Activity of Albicidin Derivatives with Variations of the Central Cyanoalanine Building Block
| Autor: | Dennis Kerwat, Siamak Semsary, Maria Seidel, Stefan Grätz, Roderich D. Süssmuth, Maria Kunert, Leonard von Eckardstein, John B. Weston, Julian Kretz |
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| Rok vydání: | 2016 |
| Předmět: |
Steric effects
Xanthomonas Stereochemistry 010402 general chemistry 01 natural sciences Biochemistry DNA gyrase Anti-Infective Agents Drug Discovery Escherichia coli Topoisomerase II Inhibitors Organic Chemicals General Pharmacology Toxicology and Pharmaceutics Threonine Pharmacology Alanine chemistry.chemical_classification 010405 organic chemistry Chemistry Organic Chemistry 0104 chemical sciences Amino acid Micrococcus luteus DNA Gyrase Molecular Medicine Pharmacophore Chirality (chemistry) Antibacterial activity Bacillus subtilis |
| Zdroj: | ChemMedChem. 11:1499-1502 |
| ISSN: | 1860-7179 |
| Popis: | To investigate the pharmacophore regions of the antibiotic albicidin, derivatives with variations on the central amino acid were synthesized. Charged as well as uncharged residues were chosen to explore the influence of charge, chirality, and steric bulk. The bioactivity of the newly synthesized derivatives was determined by a microdilution technique to obtain minimum inhibitory concentrations (MIC) values. The compounds were also tested in a cell-free system to obtain information about their ability to inhibit their primary target, DNA gyrase. It was then shown that derivatives with uncharged side chains retain antibacterial activity, whereas incorporation of charged amino acid residues decreases the antibacterial activity dramatically, possibly due to restricted cell penetration of these derivatives. From the newly synthesized derivatives, the threonine derivative shows the most promising results in both tests. The information will help to develop the features of albicidin toward more drug-like structures. |
| Databáze: | OpenAIRE |
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