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. (August 2018)

• Record Type: Journal Article
• Authors: Forget, Stephanie; Robertson, Andrew W.; Hall, Steven; MacLeod, Jeanna; Overy, David; Kerr, Russell; Goralski, Kerry; Jakeman, David
• Is Part Of: Journal of antibiotics. Volume 71:Number 8(2018:Aug.)
• Page Start: 722
• Page End: 730
• Publication Date: 2018-08
• Subjects: Antibiotics -- Periodicals; 615.329
• DOI: 10.1038/s41429-018-0060-0
• Languages: English
• ISSNs: 0021-8820

Abstract

Abstract Herein, we report the characterization and antimicrobial activity of a previously unreported jadomycin (1 ) obtained from a culture ofS. venezuelae ISP5230 withl -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 theδ -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 of1 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. Compound1 was found to produce the highest ROS activity and to possess the greatest cytotoxicity against MDA-MB-231 breast cancer cells.