Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions
Abstract
:1. Introduction
2. Mode of Action of CAM
3. Bacterial Survival Strategies to Combat CAM Activity
4. Side Effects of CAM
5. Modifications of CAM to Obtain Antibacterials with Improved Properties
5.1. Modifications of the p-Nitrophenyl Moiety
5.2. Modifications of the 2-Amino-1,3-propanediol Moiety
5.3. Modifications at Both the p-Nitrophenyl and the 2-Amino-1,3-propanediol Moieties
5.4. Modifications at the Dichloroacetyl Moiety
6. CAM Hybrids and Dimers
6.1. CAM Hybrids
6.2. CAM Heterodimers
6.3. CAM Homodimers
7. Synopsis and Future Perspectives
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Ehrlich, J.; Bartz, Q.R.; Smith, R.M.; Joslyn, D.A.; Burkholder, P.R. Chloromycetin, a new antibiotic from a soil actinomycete. Science 1947, 106, 417. [Google Scholar] [CrossRef] [PubMed]
- Pongs, O. Chloramphenicol. In Mechanism of Action of Antibacterial Agents; Hann, F.E., Ed.; Springer: New York, NY, USA, 1979; Volume 5, pp. 26–42. [Google Scholar]
- Contreras, A.; Vazquez, D. Cooperative and antagonistic interactions of peptidyl-tRNA and antibiotics with bacterial ribosomes. Eur. J. Biochem. 1977, 74, 539–547. [Google Scholar] [CrossRef] [PubMed]
- Long, K.S.; Porse, B.T. A conserved chloramphenicol binding site at the entrance to the ribosomal peptide exit tunnel. Nucleic Acids Res. 2003, 31, 7208–7215. [Google Scholar] [CrossRef] [PubMed]
- Hansen, J.L.; Moore, P.B.; Steitz, T.A. Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit. J. Mol. Biol. 2003, 330, 1061–1075. [Google Scholar] [CrossRef]
- Kostopoulou, O.N.; Magoulas, G.E.; Papadopoulos, G.E.; Mouzaki, A.; Dinos, G.P.; Papaioannou, D.; Kalpaxis, D.L. Synthesis and evaluation of chloramphenicol homodimers: Molecular target, antimicrobial activity, and toxicity against human cells. PLoS ONE 2015, 10, e0134526. [Google Scholar] [CrossRef] [PubMed]
- Pestka, S.; Le Mahieu, R.A. Inhibition of [14C] chloramphenicol binding to Escherichia coli ribosomes by erythromycin derivatives. Antimicrob. Agents Chemother. 1974, 6, 39–45. [Google Scholar] [CrossRef] [PubMed]
- Rheinberger, H.J.; Nierhaus, K.H. Partial release of AcPhe-transfer RNA from ribosomes during poly(U)-dependent poly(Phe) synthesis and the effects of chloramphenicol. Eur. J. Biochem. 1990, 193, 643–650. [Google Scholar] [CrossRef] [PubMed]
- Vester, B.; Garrett, R.A. The importance of highly conserved nucleotides in the binding region of chloramphenicol at the peptidyl transferase center of Escherichia coli 23S ribosomal RNA. EMBO J. 1988, 7, 3577–3587. [Google Scholar] [PubMed]
- Douthwaite, S. Functional interactions within 23S rRNA involving the peptidyltransferase center. J. Bacteriol. 1992, 174, 1333–1338. [Google Scholar] [PubMed]
- Giessing, A.M.; Jensen, S.S.; Rasmussen, A.; Hansen, L.H.; Gondela, A.; Long, K.; Vester, B.; Kirpekar, F. Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria. RNA 2009, 15, 327–336. [Google Scholar] [CrossRef] [PubMed]
- Persaud, C.; Lu, Y.; Vila-Sanjurjo, A.; Campell, J.L.; Finley, J.; O’Connor, M. Mutagenesis of the modified bases, m5U1939 and ψ2504, in Escherichia coli 23S rRNA. Biochem. Biophys. Res. Commun. 2010, 392, 223–227. [Google Scholar] [CrossRef] [PubMed]
- Celma, M.L.; Monro, R.E.; Vazquez, D. Substrate and antibiotic binding sites at the peptidyl transferase center of E. coli ribosomes: Binding of UACCA-leu to 50S subunits. FEBS Lett. 1971, 13, 247–251. [Google Scholar] [CrossRef]
- Fernandez-Muñoz, R.; Vazquez, D. Kinetic studies of peptide bond formation. Effect of chloramphenicol. Mol. Biol. Rep. 1973, 1, 75–79. [Google Scholar] [CrossRef] [PubMed]
- Pestka, S. The use of inhibitors in studies on protein synthesis. Methods Enzymol. 1974, 30, 261–282. [Google Scholar] [PubMed]
- Drainas, D.; Kalpaxis, D.L.; Coutsogeorgopoulos, C. Inhibition of ribosomal peptidyl transferase by chloramphenicol: Kinetic studies. Eur. J. Biochem. 1987, 164, 53–58. [Google Scholar] [CrossRef] [PubMed]
- Xaplanteri, M.; Andreou, A.; Dinos, G.P.; Kalpaxis, D.L. Effect of polyamines in the inhibition of peptidyl transferase by antibiotics: Revisiting the mechanism of chloramphenicol action. Nucleic Acids Res. 2003, 31, 5074–5083. [Google Scholar] [CrossRef] [PubMed]
- Schlünzen, F.; Zarivach, R.; Harms, J.; Bashan, A.; Tocilj, A.; Albrecht, R.; Yonath, A.; Franceschi, F. Structural basis for the interaction of antibiotics with the peptidyl transferase center in eubacteria. Nature 2001, 413, 814–821. [Google Scholar] [CrossRef] [PubMed]
- Dunkle, J.A.; ** of Escherichia coli ribosomal components involved in peptidyl transferase activity. Proc. Nat. Acad. Sci. USA 1973, 70, 1423–1426. [Google Scholar] [CrossRef] [PubMed]
- Hazra, B.G.; Pore, V.S.; Dey, S.K.; Data, S.; Darokar, M.P.; Saikia, D.; Khanuga, S.P.S.; Thakur, A.P. Bile acid amides derived from chiral amino alcohols: Novel antimicrobials and antifungals. Bioorg. Med. Chem. Lett. 2004, 14, 773–777. [Google Scholar] [CrossRef] [PubMed]
- Coutsogeorgopoulos, C. On the mechanism of action of chloramphenicol in protein synthesis. Biochim. Biophys. Acta 1966, 129, 214–217. [Google Scholar] [CrossRef]
- Vince, R.; Almquist, R.C.; Ritter, C.L.; Daluge, S. Chloramphenicol binding site with analogues of chloramphenicol and puromycin. Antimicrob. Agents Chemother. 1975, 8, 439–443. [Google Scholar] [CrossRef] [PubMed]
- McFarlan, S.C.; Vince, R. Inhibition of peptidyltransferase and possible mode of action of a dipeptidyl chloramphenicol analogue. Biochem. Biophys. Res. Commun. 1984, 122, 748–754. [Google Scholar] [CrossRef]
- Drainas, D.; Mamos, P.; Coutsogeorgopoulos, C. Aminoacyl analogs of chloramphenicol: Examination of the kinetics of inhibition of peptide bond formation. J. Med. Chem. 1993, 36, 3542–3545. [Google Scholar] [CrossRef] [PubMed]
- Michelinaki, M.; Mamos, P.; Coutsogeorgopoulos, C.; Kalpaxis, D.L. Aminoacyl and peptidyl analogs of chloramphenicol as slow-binding inhibitors of ribosomal peptidyltransferase: A new approach for evaluating their potency. Mol. Pharmacol. 1997, 51, 139–146. [Google Scholar] [PubMed]
- Johansson, D.; Jessen, C.H.; Pøhlsgaard, J.; Jensen, K.B.; Vester, B.; Pederden, E.B.; Nielsen, P. Design, synthesis and ribosome binding of chloramphenicol nucleotide and intercalator conjugates. Bioorg. Med. Chem. Lett. 2005, 15, 2079–2083. [Google Scholar] [CrossRef] [PubMed]
- Kostopoulou, O.N.; Kourelis, T.G.; Mamos, P.; Magoulas, G.E.; Kalpaxis, D.L. Insights into the chloramphenicol inhibition effect on peptidyl transferase activity, using two new analogs of the drug. Open Enz. Inhib. J. 2011, 4, 1–10. [Google Scholar] [CrossRef]
- Mamos, P.; Krokidis, M.G.; Papadas, A.; Karahalios, P.; Starosta, A.L.; Wilson, D.N.; Kalpaxis, D.L.; Dinos, P. On the use of antibiotic chloramphenicol to target polypeptide chain mimics to the ribosomal exit tunnel. Biochimie 2013, 95, 1765–1772. [Google Scholar] [CrossRef] [PubMed]
- Wilson, D.N. Peptides in the ribosomal tunnel talk back. Mol. Cell 2011, 41, 247–248. [Google Scholar] [CrossRef] [PubMed]
- Gagnon, M.G.; Roy, R.N.; Lomakin, I.B.; Florin, T.; Mankin, A.S.; Steitz, T.A. Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition. Nucleic Acids Res. 2016. [Google Scholar] [CrossRef] [PubMed]
- Nikaido, H. The role of outer membrane and efflux pumps on the resistance of Gram-negative bacteria. Can we improve drug access? Drug Resist. Updat. 1998, 1, 93–98. [Google Scholar] [CrossRef]
- Igarashi, K.; Kashiwagi, K. Characteristics of cellular polyamine transport in prokaryotes and eukaruotes. Plant Physiol. Biochem. 2010, 48, 506–512. [Google Scholar] [CrossRef] [PubMed]
- Poolin, R.; Casero, R.A.; Soulet, D. Recent advances in the molecular biology of metazoan polyamine transport. Amino Acids 2012, 42, 711–723. [Google Scholar] [CrossRef] [PubMed]
- Žemlička, J.; Bhuta, A. Sparsophenicol: A new synthetic hybrid antibiotic inhibiting peptide synthesis. J. Med. Chem. 1982, 25, 1123–1125. [Google Scholar] [CrossRef] [PubMed]
- Žemlička, J.; Fernandez-Moyano, M.C.; Ariatti, M.; Zurenko, G.E.; Grady, J.E.; Ballesta, J.P.G. Hybrids of antibiotics inhibiting protein synthesis: Synthesis and biological activity. J. Med. Chem. 1993, 36, 1239–1244. [Google Scholar] [CrossRef] [PubMed]
- Kwon, M.; Κim, H.-J.; Lee, J.; Yu, J. Enhanced binding affinity of neomycin-chloramphenicol (or linezolid) conjugates to A-site model of 16S ribosomal RNA. Bull. Korean Chem. Soc. 2006, 27, 1664–1666. [Google Scholar]
- Berkov-Zrihen, Y.; Green, K.D.; Labby, L.J.; Freldman, M.; Garneau-Tsodikova, S.; Fridman, M. Synthesis and evaluation of hetero- and homodimers of ribosome targeting antibiotics: Antimicrobial activity, in vitro inhibition of translation, and drug resistance. J. Med. Chem. 2013, 21, 3624–3631. [Google Scholar] [CrossRef] [PubMed]
- Kostopoulou, O.N.; Papadopoulos, G.; Kouvela, E.C.; Kalpaxis, D.L. Clindamycin binding to ribosomes revisited: Foοtprinting and computational detection of two binding sites within the peptidyl transferase center. Pharmazie 2013, 36, 1239–1244. [Google Scholar]
© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Dinos, G.P.; Athanassopoulos, C.M.; Missiri, D.A.; Giannopoulou, P.C.; Vlachogiannis, I.A.; Papadopoulos, G.E.; Papaioannou, D.; Kalpaxis, D.L. Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions. Antibiotics 2016, 5, 20. https://doi.org/10.3390/antibiotics5020020
Dinos GP, Athanassopoulos CM, Missiri DA, Giannopoulou PC, Vlachogiannis IA, Papadopoulos GE, Papaioannou D, Kalpaxis DL. Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions. Antibiotics. 2016; 5(2):20. https://doi.org/10.3390/antibiotics5020020
Chicago/Turabian StyleDinos, George P., Constantinos M. Athanassopoulos, Dionissia A. Missiri, Panagiota C. Giannopoulou, Ioannis A. Vlachogiannis, Georgios E. Papadopoulos, Dionissios Papaioannou, and Dimitrios L. Kalpaxis. 2016. "Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions" Antibiotics 5, no. 2: 20. https://doi.org/10.3390/antibiotics5020020