Isolation of a jadomycin incorporating l-ornithine, analysis of antimicrobial activity and jadomycin reactive oxygen species (ROS) generation in MDA-MB-231 breast cancer cells
| Autor: | Steven R. Hall, Stephanie M. Forget, Jeanna M. MacLeod, Russell G. Kerr, Andrew W. Robertson, David L. Jakeman, David P. Overy, Kerry B. Goralski |
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| Rok vydání: | 2018 |
| Předmět: |
Ornithine
Cell Survival Staphylococcus Antineoplastic Agents Triple Negative Breast Neoplasms Microbial Sensitivity Tests 010402 general chemistry 01 natural sciences Oxazolone Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery Humans Viability assay Cytotoxicity Pharmacology chemistry.chemical_classification Reactive oxygen species biology 010405 organic chemistry Chemistry Isoquinolines Antimicrobial biology.organism_classification Streptomyces Anti-Bacterial Agents 0104 chemical sciences Biochemistry Drug Resistance Neoplasm Hemiaminal Lactam Reactive Oxygen Species Bacteria |
| Zdroj: | The Journal of Antibiotics. 71:722-730 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.1038/s41429-018-0060-0 |
| Popis: | Herein, we report the characterization and antimicrobial activity of a previously unreported jadomycin (1) obtained from a culture of S. venezuelae ISP5230 with l-ornithine (Orn). 1 arises from the rearrangement of a putative five-membered ring containing jadomycin incorporating Orn, whereby intramolecular attack of the E-ring carbonyl from the δ-NH2 group of the Orn side chain results in collapse of the oxazolone ring and formation of a stable six-membered lactam. This rearrangement produces a jadomycin with a 3a hemiaminal position that is susceptible to solvolysis. A structure–activity relationship is discussed based on the antimicrobial activity of 1 compared to previously reported jadomycins, providing evidence that the presence of a 3a hemiaminal enhances activity against Gram-positive bacteria. Additionally, assays to quantify reactive oxygen species (ROS) generation and cell viability were performed using a series of nine jadomycins. Compound 1 was found to produce the highest ROS activity and to possess the greatest cytotoxicity against MDA-MB-231 breast cancer cells. |
| Databáze: | OpenAIRE |
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