Abstract
Chloramphenicol (CAM) is the D-threo isomer of a small molecule, consisting of a p-nitrobenzene ring connected to a dichloroacetyl tail through a 2-amino-1,3-propanediol moiety. CAM displays a broad-spectrum bacteriostatic activity by specifically inhibiting the bacterial protein synthesis. In certain but important cases, it also exhibits bactericidal activity, namely against the three most common causes of meningitis, Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Resistance to CAM has been frequently reported and ascribed to a variety of mechanisms. However, the most important concerns that limit its clinical utility relate to side effects such as neurotoxicity and hematologic disorders. In this review, we present previous and current efforts to synthesize CAM derivatives with improved pharmacological properties. In addition, we highlight potentially broader roles of these derivatives in investigating the plasticity of the ribosomal catalytic center, the main target of CAM.
Highlights
Sixty decades of biochemical studies and more recent crystallographic studies, have revealed the molecular basis by which chloramphenicol (CAM) inhibits bacterial protein synthesis.CAM is an old broad-spectrum antibiotic but its medical and veterinary applications as antibacterial are full of pros and cons
Upon CAM discovery [1], it was recognized that the D-threo isomer (Figure 1) inhibits bacterial protein synthesis
May induce expression of efflux pumps, such as MexXY in Pseudomonas aeruginosa that belongs to resistance nodulation and cell division (RND) family [53] or enhance the efflux of other ligands by AcrB pump in E. coli [54]
Summary
Sixty decades of biochemical studies and more recent crystallographic studies, have revealed the molecular basis by which chloramphenicol (CAM) inhibits bacterial protein synthesis. CAM is an old broad-spectrum antibiotic but its medical and veterinary applications as antibacterial are full of pros and cons. Besides resistance to CAM frequently reported, the major disinclined concerns for the clinical use of CAM relate to the side effects in long antibiotic courses causing neurotoxicity and hematologic disorders. This has prompted many investigators to attempt the synthesis of new CAM derivatives with improved pharmaceutical properties. CAM derivatives have contributed to compacting resistant bacteria and addressing side effects of the drug.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
