24863-80-7Relevant articles and documents
Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics
Nasrin, Shamima,Ganji, Suresh,Kakirde, Kavita S.,Jacob, Melissa R.,Wang, Mei,Ravu, Ranga Rao,Cobine, Paul A.,Khan, Ikhlas A.,Wu, Cheng-Cang,Mead, David A.,Li, Xing-Cong,Liles, Mark R.
, p. 1321 - 1332 (2018/06/29)
A functional metagenomic approach identified novel and diverse soil-derived DNAs encoding inhibitors to methicillin-resistant Staphylococcus aureus (MRSA). A metagenomic DNA soil library containing 19 200 recombinant Escherichia coli BAC clones with 100 Kb average insert size was screened for antibiotic activity. Twenty-seven clones inhibited MRSA, seven of which were found by LC-MS to possess modified chloramphenicol (Cm) derivatives, including three new compounds whose structures were established as 1-acetyl-3-propanoylchloramphenicol, 1-acetyl-3-butanoylchloramphenicol, and 3-butanoyl-1-propanoylchloramphenicol. Cm was used as the selectable antibiotic for cloning, suggesting that heterologously expressed enzymes resulted in derivatization of Cm into new chemical entities with biological activity. An esterase was found to be responsible for the enzymatic regeneration of Cm, and the gene trfA responsible for plasmid copy induction was found to be responsible for inducing antibacterial activity in some clones. Six additional acylchloramphenicols were synthesized for structure and antibacterial activity relationship studies, with 1-p-nitrobenzoylchloramphenicol the most active against Mycobacterium intracellulare and Mycobacterium tuberculosis, with MICs of 12.5 and 50.0 μg/mL, respectively.
Synthesis and antimicrobial activity of chloramphenicol-polyamine conjugates
Magoulas, George E.,Kostopoulou, Ourania N.,Garnelis, Thomas,Athanassopoulos, Constantinos M.,Kournoutou, Georgia G.,Leotsinidis, Michael,Dinos, George P.,Papaioannou, Dionissios,Kalpaxis, Dimitrios L.
, p. 3163 - 3174 (2015/08/03)
Abstract A series of chloramphenicol (CAM) amides with polyamines (PAs), suitable for structure-activity relationship studies, were synthesized either by direct attachment of the PA chain on the 2-aminopropane-1,3-diol backbone of CAM, previously oxidized selectively at its primary hydroxyl group, or from chloramphenicol base (CLB) through acylation with succinic or phthalic anhydride and finally coupling with a PA. Conjugates 4 and 5, in which the CLB moiety was attached on N4 and N1 positions, respectively, of the N8,N8-dibenzylated spermidine through the succinate linker, were the most potent antibacterial agents. Both conjugates were internalized into Escherichia coli cells by using the spermidine-preferential uptake system and caused decrease in protein and polyamine content of the cells. Noteworthy, conjugate 4 displayed comparable activity to CAM in MRSA or wild-type strains of Staphylococcus aureus and Escherichia coli, but superior activity in E. coli strains possessing ribosomal mutations or expressing the CAM acetyltransferase (cat) gene. Lead compounds, and in particular conjugate 4, have been therefore discovered during the course of the present work with clinical potential.
Isolation of 3' -O-acetylchloramphenicol: a possible intermediate in chloramphenicol biosynthesis.
Gross, Frank,Lewis, Elizabeth A,Piraee, Mahmood,van Pee, Karl-Heinz,Vining, Leo C,White, Robert L
, p. 283 - 286 (2007/10/03)
3' -O-acetylchloramphenicol, commonly formed from chloramphenicol by resistant bacteria, has been isolated from the antibiotic-producing organism. Biosynthetic experiments suggest that it is a protected intermediate in chloramphenicol biosynthesis, implicating acetylation as a self-resistance mechanism in the producing organism.
