Chloramphenicol derivatives as antibacterial and anticancer agents: Historic problems and current solutions

Antibiotics

Volumn 5, Issue 2, 2016, Pages

  Dinos, George P ^a   Athanassopoulos, Constantinos M ^b   Missiri, Dionissia A ^b   Giannopoulou, Panagiota C ^a   Vlachogiannis, Ioannis A ^a   Papadopoulos, Georgios E ^c   Papaioannou, Dionissios ^b   Kalpaxis, Dimitrios L ^a  

^a UNIVERSITY OF PATRAS   (Greece)

^b UNIVERSITY OF PATRAS   (Greece)

^c UNIVERSITY OF THESSALY   (Greece)

Author keywords

Antibiotic resistance; Antibiotics; Anticancer agents; Chemical synthesis; Chloramphenicol; Peptidyl transferase; Puromycin reaction; Ribosome; Side effects; Translation

Indexed keywords

1,3 DIACETYL CHLORAMPHENICOL; 3 ACETYL CHLORAMPHENICOL; ALPHA DICHLOROACETAMIDO ALPHA METHYLENE PARA NITROACETOPHENONE; BROMO NICETIN; CETOPHENICOL; CHLORAMPHENICOL DERIVATIVE; CHLORAMPHENICOL HEMISUCCINATE; CHLORAMPHENICOL PALMITATE; CHLORAMPHENICOL SPEARMINE; COLLAGENASE 3; FLORFENICOL; HETERODIMER; HOMODIMER; LINCOPHENICOL; MULTIDRUG AND TOXIN EXTRUSION PROTEIN 1; NICETIN; SPARSOPHENICOL; TEVENEL; THIAMPHENICOL; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC SENSITIVITY; ANTINEOPLASTIC ACTIVITY; BACTERIAL SURVIVAL; CELL INVASION; CHEMICAL MODIFICATION; DNA DAMAGE; GENE MUTATION; IMMUNE DEFICIENCY; IMMUNE RESPONSE; MULTIDRUG RESISTANCE; NONHUMAN; PRIORITY JOURNAL; PROTEIN SYNTHESIS INHIBITION; REVIEW;

EID: 85017880069     PISSN: None     EISSN: 20796382     Source Type: Journal    
DOI: 10.3390/antibiotics5020020     Document Type: Review

References (116)

1. 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.
2. 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.
3. Contreras, A.; Vazquez, D. Cooperative and antagonistic interactions of peptidyl-tRNA and antibiotics with bacterial ribosomes. Eur. J. Biochem. 1977, 74, 539–547.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Douthwaite, S. Functional interactions within 23S rRNA involving the peptidyltransferase center. J. Bacteriol. 1992, 174, 1333–1338.
11. 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.
12. Persaud, C.; Lu, Y.; Vila-Sanjurjo, A.; Campell, J.L.; Finley, J.; O’Connor, M. Mutagenesis of the modified bases, m5U1939 and 2504, in Escherichia coli 23S rRNA. Biochem. Biophys. Res. Commun. 2010, 392, 223–227.
13. 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.
14. Fernandez-Muñoz, R.; Vazquez, D. Kinetic studies of peptide bond formation. Effect of chloramphenicol. Mol. Biol. Rep. 1973, 1, 75–79.
15. Pestka, S. The use of inhibitors in studies on protein synthesis. Methods Enzymol. 1974, 30, 261–282.
16. Drainas, D.; Kalpaxis, D.L.; Coutsogeorgopoulos, C. Inhibition of ribosomal peptidyl transferase by chloramphenicol: Kinetic studies. Eur. J. Biochem. 1987, 164, 53–58.
17. 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.
18. 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.
19. Dunkle, J.A.; Xiong, L.; Mankin, A.S.; Cate, J.H.D. Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action. Proc. Natl. Acad. Sci. USA 2010, 107, 17152–17157.
20. Bulkley, D.; Innis, C.A.; Blaha, G.; Steitz, T.A. Revisiting the structures of several antibiotics bound to the bacterial ribosome. Proc. Natl. Acad. Sci. USA 2010, 107, 17158–17163.
21. Kirillov, S.V.; Porse, B.T.; Garrett, R.A. Peptidyl transferase antibiotics perturb the relative positioning of the 31-terminal adenosine of P/P1-site-bound tRNA and 23S rRNA in the ribosome. RNA 1999, 5, 1003–1013.
22. Cheney, B.V. Ab initio calculations on the large molecules using molecular fragments. Structural correlations between natural moieties and some antibiotic inhibitors of peptidyl transferase. J. Med. Chem. 1974, 17, 590–599.
23. Bhuta, P.; Chung, H.L.; Hwang, J.-S.; Žemliˇcka, J. Analogues of chloramphenicol: Circular dichroism spectra, inhibition of ribosomal peptidyl tranferase, and possible mechanism of action. J. Med. Chem. 1980, 23, 1299–1305.
24. Goodman, M.; Chorev, M. On the concept of linear modified retro-peptide structures. Acc. Chem. Res. 1979, 12, 1–7.
25. Monro, R.E.; Staehelin, T.; Celma, M.L.; Vazquez, D. The peptidyl transferase activity of ribosomes. Cold Spring Harb. Symp. Quant. Biol. 1969, 34, 357–368.
26. Pestka, S. Studies on the formation of transfer ribonucleic acid-ribosome complexes. Survey of the effect of antibiotics of N-acetyl-phenylalanine-puromycine formation: Possible mechanism of chloramphenicol action. Arch. Biochem. Biophys. 1970, 136, 80–88.
27. Kalpaxis, D.L.; Coutsogeorgopoulos, C. Type of inhibition of peptide bond formation by chloramphenicol depends on the temperature and the concentration of ammonium ions. Mol. Pharmacol. 1989, 36, 615–619.
28. Morrison, J.B.; Walsh, C.T. The behavior and significance of slow-binding enzyme inhibitors. Adv. Enzymol. Relat. Areas Mol. Biol. 1988, 61, 201–301.
29. Pestka, S. Studies on the formation of transfer ribonucleic acid-ribosome complexes. XI. Antibiotic effects on phenylalanine-oligonucleotide binding to ribosomes. Proc. Natl. Acad. Sci. USA 1969, 64, 709–714.
30. Polacek, N.; Gomez, M.J.; Ito, K.; Xiong, L.; Nakamura, Y.; Mankin, A.S. The critical role of universally conserved A2602 of 23S ribosomal RNA in the release of the nascent peptide during translation termination. Mol. Cell 2003, 11, 103–112.
31. Thompson, J.; O’Connor, M.; Mills, J.A.; Dahlberg, A.E. The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause extensive translational inaccuracy in vivo. J. Mol. Biol. 2002, 322, 273–279.
32. Champey, W.S. The other target for ribosomal antibiotics inhibition of bacterial subunit formation. Infect. Disord. Drug Targets 2006, 6, 377–390.
33. Silback, T.; Peil, L.; Xiong, L.; Mankin, A.; Remme, J.; Tenson, T. Erythromycin- and chloramphenicol-induced ribosomal assembly defects are secondary effects of protein synthesis inhibition. Antimicrob. Agents Chemother. 2009, 53, 563–571.
34. Brown, E.D.; Wright, G.D. Antibacterial drug discovery in the resistance era. Nature 2016, 529, 336–343.
35. Osawa, S.; Takata, R. Chloramphenicol resistant mutants of Bacillus subtilis. Mol. Gen. Genet. 1973, 127, 163–173.
36. Ma, L.; Shen, Z.; Naren, G.; Li, H.; Xia, X.; Wu, C.; Shen, J.; Zhang, Q.; Wang, Y. Identification of a novel G2073A mutation in 23S rRNA in amphenicol-selected mutants of Campylobacter jejuni. PLoS ONE 2014, 9, e94503.
37. Schwarz, S.; Kehrenberg, C.; Doublet, B.; Cloeckaert, A. Molecular basis of bacterial resistance to chloramphenicol and florfenicol. FEMS Microbiol. Rev. 2004, 28, 519–542.
38. Mosher, R.H.; Camp, D.J.; Yang, K.; Brown, M.P.; Shaw, W.W.; Vining, L.C. Inactivation of chloramphenicol by O-phosphorylation. J. Biol. Chem. 1995, 27, 27000–27006.
39. Izard, T.; Ellis, J. The crystal structure of chloramphenicol phosphotransferase reveals a novel inactivation mechanism. EMBO J. 2000, 19, 2690–2700.
40. Rajesh, T.; Sung, C.; Kim, H.; Song, E.; Park, H.Y.; Jeon, J.M.; Yoo, D.; Kim, H.J.; Kim, Y.H.; Choi, K.Y., et al. Phosphorylation of chloramphenicol by a recombinant protein Yhr2 from Streptomyces avermitilis MA4680. Bioorg. Med. Chem. Lett. 2013, 23, 3614–3619.
41. Mosher, R.H.; Ranade, N.P.; Schrempf, H.; Vining, L.C. Chloramphenicol resistance in Streptomyces, cloning and characterization of a chloramphenicol hydrolase gene from Streptomyces venezuelae. J. Gen. Microbiol. 1990, 136, 293–301.
42. Tao, W; Lee, M.H.; Wu, J.; Kim, N.H.; Kim, J.-C.; Chung, E.; Hwang, E.C.; Lee, S.-W. Inactivation of chloramphenicol and florfenicol by a novel chloramphenicol hydrolase. Appl. Environ. Microbiol. 2012, 28, 6295–6301.
43. Smith, A.L.; Erwin, A.L.; Kline, T.; Unrath, W.C.; Nelson, K.; Weber, A.; Howard, W.N. Chloramphenicol is a substrate for a novel nitroreductase pathway in Heamophila influenzae. Antimicrob. Agents Chemother. 2007, 51, 2820–2829.
44. Delcour, A.H. Outer membrane permeability and antibiotic resistance. Biochim. Biophys. Acta 2009, 1794, 808–816.
45. Danilchanka, O.; Pavienok, M.; Niederweis, M. Role of porins for uptake of antibiotics by Mycobacterium smegmatis. Antimicrob. Agents Chemother. 2008, 52, 3127–3134.
46. Kadlec, K.; Kerhrenberg, C.; Schwarz, S. Efflux-mediated resistance to florfenicol and/or chloramphenicol in Bordetella bronchiseptica: Identification of a novel chloramphenicol exporter. J. Antimicrob. Chemoth. 2007, 59, 191–196.
47. Liu, H.; Wang, Y.; Wu, C.; Schwarz, S.; Shen, Z.; Jeon, B.; Ding, S.; Zhang, Q.; Shen, J. A novel phenicol exporter gene, fexB, found in enterococci of animal origin. J. Antimicrob. Chemother. 2012, 67, 322–325.
48. Fluman, N.; Bibi, E. Bacterial multidrug transport through the lens of the major facilitator superfamily. Biochim. Biophys. Acta 2009, 1794, 738–747.
49. Bay, D.C.; Rommens, K.L.; Turner, R.J. Small multidrug resistance proteins: A multidrug transporter family that continues to grow. Biochim. Biophys. Acta 2008, 1778, 1814–1838.
50. Magnet, S.; Courvalin, P.; Lambert, T. Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrob. Agents Chemother. 2001, 45, 3375–3380.
51. Jones, P.M.; George, A.M. The ABC transporter structure and mechanism: Perspectives on recent research. Cell. Mol. Life Sci. 2004, 61, 682–699.
52. Kuroda, T.; Tsuchiya, T. Multidrug efflux transporters in the MATE family. Biochim. Biophys. Acta 2009, 1794, 763–768.
53. Jeannot, K.; Sobel, M.L.; Garch, F.F.; Poole, K.; Plesiat, P. Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction. J. Bacteriol. 2005, 187, 5341–5346.
54. Kinama, A.D.; Yargiu, A.Y.; Nikaido, H. Some ligands enhance the efflux of other ligands by the Escherichia coli multi drug pump AcrB. Biochemistry 2013, 52, 8342–8351.
55. Ersler, A.J.; Iossifides, I.A. In vitro action of chloramphenicol-analogues on the metabolism of human red blood cells. Acta Haemat. 1962, 28, 1–19.
56. Yunis, A.A.; Arimura, G.K.; Isildar, M. DNA damage induced by chloramphenicol and its nitroso derivative: Damage in intact cells. Am. J. Hematol. 1987, 24, 77–84.
57. Krajewska, D.; Dabrowska, M.; Jakoniuk, P.; Rózánski, A. Pyrrole analogues of chloramphenicol. I. Synthesis and antibacterial activity of DL-threo-1-(l-methyl-4-nitro-pyrrole-2-yl)-2-dichloroacetamidopropane-1,3-diol. Acta Pol. Pharm. 2000, 57, 213–221.
58. Ohnisi, S.; Murata, M.; Ida, N.; Oikawa, S.; Kawanishi, S. Oxidative DNA damage induced by metabolites of chloramphenicol, an antibiotic drug. Free Radic. Res. 2015, 49, 1165–1172.
59. Yunnis, A.A. Chloramphenicol-induced bone marrow suppression. Semin. Hematol. 1973, 10, 225–234.
60. Jones, C.N.; Miller, C.; Tenenbaum, A.; Spremmuli, L.L.; Saada, A. Antibiotic effects on mitochondrial translation and in patients with mitochondrial translation defects. Mitochondrion 2009, 9, 429–437.
61. Ott, M.; Amunts, A.; Brown, A. Organization and regulation of mitochondrial protein synthesis. Annu. Rev. Biochem. 2016, 85.
62. Turton, J.A.; Fagg, R.; Sones, W.R.; Williams, T.C.; Andrews, C.M. Characterization of the myelotoxicity of chloramphenicol succinate in the B6C3F1 mouse. Int. J. Exp. Pathol. 2006, 87, 101–112.
63. Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 2001, 46, 3–26.
64. Nau, R.; Sörgel, F.; Eiffert, H. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. Clin. Microbiol. Rev. 2010, 23, 858–883.
65. Musa, S.H.; Basri, M.; Masoumi, H.R.; Karjiban, R.A.; Malek, E.A.; Basri, H.; Shamsuddin, A.F. Formulation optimization of palm kernel oil esters nanoemulsion-loaded with chloramphenicol suitable for meningitis treatment. Colloids Surf. B Biointerfaces 2013, 112, 113–119.
66. Wang, M.Y.; Sadum, A.A. Drug-related mitochondrial optic neuropathies. J. Neuroophthalmol. 2013, 33, 172–178.
67. Sachs, B.; Erdmann, T.; Al Masaoudi, T.; Merk, H.F. Molecular features determining hymphocyte reactivity in allergic contact dermatitis to chloramphenicol and azidamphenicol. Allergy 2001, 56, 69–72.
68. Shuang, G.; Yu, S.; Guo, W.; Wang, D.; Zhang, Z.; Lu, J.; Deng, X. Immunosupressive activity of florfenicol on the immune responses in mice. Immunol. Invest. 2011, 40, 356–366.
69. McIntype, J.; Choonara, I. Drug toxicity in the neonate. Biol. Neonate 2004, 86, 218–221.
70. Li, C.H.; Cheng, Y.W.; Liao, P.L.; Yang, Y.T.; Kang, J.J. Chloramphenicol causes mitochondrial stress, decreases ATP biosynthesis, induces matrix metalloproteinase-13 expression, and solid-tumor invasion. Toxicol. Sci. 2010, 116, 140–150.
71. Lamb, R.; Ozsvari, B.; Lisanti, C.L.; Tanowitz, H.B.; Howell, A.; Martinez-Outschoorn, U.E.; Sotgia, F.; Lisanti, M.P. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease. Oncotarget 2015, 6, 4569–4584.
72. Lokhande, J.; Juvekar, A.S.; Kulkarni, K.P. Chloramphenicol: Screening and review to evaluate the potential beneficial effects in leukaemia. J. Indian Med. Assoc. 2007, 105, 224–228.
73. Kostopoulou, O.N.; Kouvela, E.C.; Magoulas, G.E.; Garnelis, T.; Panagoulias, I.; Rodi, M.; Papadopoulos, G.; Mouzaki, A.; Dinos, G.P.; Papaioannou, D., et al. Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol. Nucleic Acids Res. 2014, 42, 8621–8634.
74. Yuan, Z.R.; Shi, Y. Chloramphenicol induces abnormal differentiation and inhibits apoptosis in activated T cells. Cancer Res. 2008, 68, 4875–4881.
75. Ziebell, G.; Gross, H.; Bladler, G. Synthesis and antibacterial activity of perchlorylchloramphenicol. Pharmazie 1983, 38, 587–589.
76. Yunis, A.A.; Manyan, D.R.; Arimura, G.K. Comparative effect of chloramphenicol and thiamphenicol on DNA and mitochondrial protein synthesis in mammalian cells. J. Lab. Clin. Med. 1973, 81, 713–718.
77. Mullen, G.B.; Georgiev, V.S. Adamantylmethyl analogues of chloramphenicol. J. Pharm. Sci. 1988, 77, 643–644.
78. Davis, T.D.; Gerry, C.J.; Tan, D.S. General platform for systematic quantitative evaluation of small molecule permeability in bacteria. ACS Chem. Biol. 2014, 9, 2535–2544.
79. Krajewska, D.; Dabrowska, M.; Jakoniuk, P.; Róza´ nski, A. Pyrrole analogues of chloramphenicol. III. Synthesis and antibacterial activity of DL-threo-1-(1-methyl-sulfonyl]pyrrole-3-yl)-2-dichlorocyclopropane-1,3-diol. Acta Pol. Pharm. 2002, 59, 127–132.
80. Ambrose, P.J. Clinical pharmacokinetics of chloramphenicol and chloramphenicol succinate. Clin. Pharmacokinet. 1984, 9, 222–238.
81. Brady, A.J.; Gray, J.D. The treatment of fungous infection of the skin with nicetin. Can. Med. Assoc. J. 1957, 76, 725–729.
82. Kono, M.; O’Hara, K.; Honda, M.; Mitsuhashi, S. Drug resistance of Staphylococci. XI. Induction of chloramphenicol resistance by its derivatives and analogues. J. Antibiot. (Tokyo) 1969, 22, 603–607.
83. Hahn, F.E. New derivatives of chloramphenicol active against resistant bacteria. Naturwissenschaften 1980, 67, 89–90.
84. Magoulas, G.E.; Kostopoulou, O.N.; Garnelis, T.; Athanassopoulos, C.M.; Kournoutou, G.G.; Leotsinidis, M.; Dinos, G.P.; Papaioannou, D.; Kalpaxis, D.L. Synthesis and antimicrobial activity of chloramphenicol-polyamine conjugates. Bioorg. Med. Chem. 2015, 23, 3163–3174.
85. Piffaretti, J.C.; Allet, B.; Pitton, J.S. Analogy between in vivo and in vitro biological effect of chloramphenicol and its acetylated derivatives. FEBS Lett. 1970, 11, 26–28.
86. Neu, H.C.; Fu, K.P. In vitro activity of chloramphenicol and thiamphenicol analogs. Antimicrob. Agents Chemother. 1980, 18, 311–316.
87. Syriopoulou, V.P.; Harding, A.L.; Goldman, D.A.; Smith, A.L. In vitro antibacterial activity of fluorinated analogues of chloramphenicol and thiamphenicol. Antimicrob. Agents Chemother. 1981, 19, 294–297.
88. Graham, R.; Palmer, D.; Pratt, B.C.; Hart, C.A. In vitro activity of florfenicol. Eur. J. Clin. Microbiol. Infect. Dis. 1988, 7, 691–694.
89. Du, X.; Xia, C.; Shen, J.; Wu, B.; Shen, Z. Characterization of florfenicol resistance among calf pathogenic Escherichia coli. FEMS Microbiol. Lett. 2004, 236, 183–189.
90. Braibant, M.; Chevalier, J.; Chaslus-Dancla, E.; Pages, J.-M.; Cloeckaert, A. Structural and functional study of the phenicol-specific efflux pump floR belonging to the major facilitator superfamily. Antimicrob. Agents Chemother. 2005, 49, 2965–2971.
91. Doublet, B.; Schwarz, S.; Kehrenberg, C.; Cloeckaert, A. Florfenicol resistance gene floR is part of a novel transposon. Antimicrob. Agents Chemother. 2005, 49, 2106–2108.
92. Kehrenberg, C.; Schwarz, S. FexA, a novel Staphylococcus lentus gene encoding resistance to florphenicol and chloramphenicol. Antimicrob. Agents Chemother. 2004, 48, 615–618.
93. Kehrenberg, C.; Schwarz, S.; Jacobsen, L.; Hansen, L.H.; Vester, B. A new mechanism for chloramphenicol, florphenicol and clindamycin resistance: Methylation of 23S ribosomal RNA at A2503. Mol. Microbiol. 2005, 57, 1064–1073.
94. De Craene, B.A.; Deprez, P.; H’Haese, E.; Nelis, H.J.; Van den Bossche, W.; De Leenheer, P. Pharmacokinetics of florphenicol in cerebrospinal fluid and plasma of calves. Antimicrob. Agents Chemother. 1997, 41, 1991–1995.
95. Freeman, K.B. Action of the N-trifluoroacetyl analogue of D-chloramphenicol. Antimicrob. Agents Chemother. 1977, 11, 563–565.
96. Butler, P.D.; Sims, P.F.; Wild, D.G. Effects of iodoaphenicol on ribosome assembly in two strains of Escherichia coli. J. Gen. Microbiol. 1982, 128, 997–1001.
97. Sonenberg, N.; Wilchekt, M.; Zamir, A. Mapping of Escherichia coli ribosomal components involved in peptidyl transferase activity. Proc. Nat. Acad. Sci. USA 1973, 70, 1423–1426.
98. 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.
99. Coutsogeorgopoulos, C. On the mechanism of action of chloramphenicol in protein synthesis. Biochim. Biophys. Acta 1966, 129, 214–217.
100. 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.
101. 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.
102. 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.
103. 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.
104. 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.
105. 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.
106. 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.
107. Wilson, D.N. Peptides in the ribosomal tunnel talk back. Mol. Cell 2011, 41, 247–248.
108. 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.
109. 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.
110. Igarashi, K.; Kashiwagi, K. Characteristics of cellular polyamine transport in prokaryotes and eukaruotes. Plant Physiol. Biochem. 2010, 48, 506–512.
111. Poolin, R.; Casero, R.A.; Soulet, D. Recent advances in the molecular biology of metazoan polyamine transport. Amino Acids 2012, 42, 711–723.
112. Žemliˇcka, J.; Bhuta, A. Sparsophenicol: A new synthetic hybrid antibiotic inhibiting peptide synthesis. J. Med. Chem. 1982, 25, 1123–1125.
113. Žemliˇcka, 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.
114. Kwon, M.; Kim, 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.
115. 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.
116. Kostopoulou, O.N.; Papadopoulos, G.; Kouvela, E.C.; Kalpaxis, D.L. Clindamycin binding to ribosomes revisited: Footprinting and computational detection of two binding sites within the peptidyl transferase center. Pharmazie 2013, 36, 1239–1244.