Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions.
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.
Department of Biochemistry, School of Medicine, University of Patras, GR-26504 Patras, Greece. dinosg@upatras.gr.
George P
GP
Dinos
Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece. kath@chemistry.upatras.gr.
Constantinos M
CM
Athanassopoulos
Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece. dionysia.misiri@gmail.com.
Dionissia A
DA
Missiri
Department of Biochemistry, School of Medicine, University of Patras, GR-26504 Patras, Greece. bio3320@upnet.gr.
Panagiota C
PC
Giannopoulou
Department of Biochemistry, School of Medicine, University of Patras, GR-26504 Patras, Greece. vlacho.giannis92@gmail.com.
Ioannis A
IA
Vlachogiannis
Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26, GR-41221 Larissa, Greece. geopap@uth.gr.
Georgios E
GE
Papadopoulos
Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece. dapapaio@upatras.gr.
Dionissios
D
Papaioannou
Department of Biochemistry, School of Medicine, University of Patras, GR-26504 Patras, Greece. dimkal@med.upatras.gr.
Dimitrios L
DL
Kalpaxis
antibiotic resistance; antibiotics; anticancer agents; chemical synthesis; chloramphenicol; peptidyl transferase; puromycin reaction; ribosome; side effects; translation