864529-25-9Relevant academic research and scientific papers
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.
supporting information, 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.
Derivatives of Ribosome-Inhibiting Antibiotic Chloramphenicol Inhibit the Biosynthesis of Bacterial Cell Wall
Louzoun Zada, Sivan,Green, Keith D.,Shrestha, Sanjib K.,Herzog, Ido M.,Garneau-Tsodikova, Sylvie,Fridman, Micha
, p. 1121 - 1129 (2018/07/25)
Here, we describe the preparation and evaluation of α,β-unsaturated carbonyl derivatives of the bacterial translation inhibiting antibiotic chloramphenicol (CAM). Compared to the parent antibiotic, two compounds containing α,β-unsaturated ketones (1 and 4) displayed a broader spectrum of activity against a panel of Gram-positive pathogens with a minimum inhibitory concentration range of 2-32 μg/mL. Interestingly, unlike the parent CAM, these compounds do not inhibit bacterial translation. Microscopic evidence and metabolic labeling of a cell wall peptidoglycan suggested that compounds 1 and 4 caused extensive damage to the envelope of Staphylococcus aureus cells by inhibition of the early stage of cell wall peptidoglycan biosynthesis. Unlike the effect of membrane-disrupting antimicrobial cationic amphiphiles, these compounds did not rapidly permeabilize the bacterial membrane. Like the parent antibiotic CAM, compounds 1 and 4 had a bacteriostatic effect on S. aureus. Both compounds 1 and 4 were cytotoxic to immortalized nucleated mammalian cells; however, neither caused measurable membrane damage to mammalian red blood cells. These data suggest that the reported CAM-derived antimicrobial agents offer a new molecular scaffold for development of novel bacterial cell wall biosynthesis inhibiting antibiotics.
Correlation between antigen-combining-site structures and functions within a panel of catalytic antibodies generated against a single transition state analog
Fujii, Ikuo,Tanaka, Fujie,Miyashita, Hideaki,Tanimura, Ryuji,Kinoshita, Keiko
, p. 6199 - 6209 (2007/10/02)
The diversity of the immune response, which can provide a panel of catalytic antibodies with varying degrees of catalytic activity and substrate specificity by immunization with a single hapten, raises the question concerning the extent to which a rationa
