The design of novel classes of macrolides for neutrophil-dominated inflammatory diseases

Future Medicinal Chemistry

Volumn 6, Issue 6, 2014, Pages 657-674

  Haber, Vesna Eraković ^a   Bosnar, Martina ^a   Kragol, Goran ^a  

^a Xylon Doo   (Croatia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFLAMMATORY AGENT; MACROLIDE; ANTIINFECTIVE AGENT;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ASTHMA; BRONCHIOLITIS; BRONCHIOLITIS OBLITERANS; CHRONIC OBSTRUCTIVE LUNG DISEASE; DIFFUSE PANBRONCHIOLITIS; DRUG CLASSIFICATION; DRUG MECHANISM; DRUG SCREENING; DRUG STRUCTURE; EVIDENCE BASED MEDICINE; HUMAN; IMMUNOMODULATION; INFLAMMATORY DISEASE; LUNG FIBROSIS; NEUTROPHIL; NEUTROPHIL DOMINATED INFLAMMATORY DISEASE; PRIORITY JOURNAL; REVIEW; ANIMAL; BRONCHIECTASIS; CHEMISTRY; CYSTIC FIBROSIS; DRUG DESIGN; DRUG EFFECTS; IMMUNOLOGY; PATHOLOGY; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE;

ANIMALS; ANTI-BACTERIAL AGENTS; ANTI-INFLAMMATORY AGENTS; ASTHMA; BRONCHIECTASIS; CYSTIC FIBROSIS; DRUG DESIGN; HUMANS; MACROLIDES; NEUTROPHILS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE;

EID: 84902078181     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.14.14     Document Type: Review

References (114)

1. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 13(3), 159-175 (2013).
2. Henry KM, Pase L, Ramos-Lopez CF, Lieschke GJ, Renshaw SA, Reyes-Aldasoro CC. PhagoSight: an open-source MATLABR package for the analysis of fluorescent neutrophil and macrophage migration in a zebrafish model. PLoS ONE 8(8), e72636 (2013).
3. Singh SK, Sethi S, Aravamudhan S, Kruger M, Grabher C. Proteome mapping of adult zebrafish marrow neutrophils reveals partial cross species conservation to human peripheral neutrophils. PLoS ONE 8(9), e73998 (2013).
4. Macdowell AL, Peters SP. Neutrophils in asthma. Curr. Allergy Asthma Rep. 7(6), 464-468 (2007).
5. Geering B, Stoeckle C, Conus S, Simon H-U. Living and dying for inflammation: Neutrophils, eosinophils, basophils. Trends Immunol. 34(8), 1-12 (2013).
6. Tzortzaki EG, Papi A, Neofytou E, Soulitzis N, Siafakas NM. Immune and genetic mechanisms in COPD: possible targets for therapeutic interventions. Curr. Drug Targets 14(2), 141-148 (2013).
7. Verleden SE, Vandermeulen E, Ruttens D et al. Neutrophilic reversible allograft dysfunction (NRAD) and restrictive allograft syndrome (RAS). Semin. Respir. Crit. Care Med. 34(3), 352-360 (2013).
8. Dhooghe B, Noel S, Huaux F, Leal T. Lung inflammation in cystic fibrosis: Pathogenesis and novel therapies. Clin. Biochem. doi:10.1016/j.clinbiochem. 2013.12.020 (2013) (Epub ahead of print ).
9. McKinley L, Alcorn JF, Peterson A et al. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J. Immunol. 181(6), 4089-4097 (2008).
10. Tintinger GR, Anderson R, Feldman C. Pharmacological approaches to regulate neutrophil activity. Semin. Immunopathol. 35(4), 395-409 (2013).
11. Y'S Therapeutics Co Ltd: WO2009023196 (2009).
12. Zambon Group S.P.A.: WO2007003422 (2007).
13. GlaxoSmithKline Research Centre Zagreb d.o.o.: WO2006077501 (2006).
14. Basilea Pharmaceutica Ag.: WO2009098320 (2009).
15. Basilea Pharmaceutica Ag.: WO2011018510 (2011).
16. Zambon Group S.P.A.: WO2008072034 (2008).
17. Tarran R, Sabater JR, Clarke TC et al. Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion. Am. J. Physiol. Lung Cell. Mol. Physiol. 304(11), L746-L756 (2013).
18. Mencarelli A, Distrutti E, Renga B et al. Development of non-antibiotic macrolide that corrects inflammation-driven immune dysfunction in models of inflammatory bowel diseases and arthritis. Eur. J. Pharmacol. 665, 29-39 (2011).
19. Glaxo Group Ltd: WO2011131749 (2011).
20. Bosnar M, Kragol G, Kostrun S et al. et al. N′-sub-2′-O, 3′-Ncarbonimidoyl bridged macrolides: novel anti-inflammatory macrolides without antimicrobial activity. J. Med. Chem. 55, 6111-6123 (2012).
21. GlaxoSmithKline Research Centre Zagreb d.o.o.: WO2006087644 (2007).
22. GlaxoSmithKline Research Centre Zagreb d.o.o.: WO2010086349 (2010).
23. Merckle Gmbh.: WO2007012464 (2007).
24. GlaxoSmithKline Research Centre Zagreb d.o.o.: WO2006092739 (2006).
25. Tomaškovi L, Komac M, Makaruha Stegi Oet al. Macrolactonolides: a novel class of anti-inflammatory compounds. Bioorg. Med. Chem. 21(1), 321-332 (2013).
26. Yoshida K, Sunazuka T, Nagai K et al. Macrolides with promotive activity of monocyte to macrophage differentiation. J. Antibiot. (Tokyo) 58(1), 79-81 (2005).
27. Desaki M, Okazaki H, Sunazuka T, Omura S, Yamamoto K, Takizawa H. Molecular mechanisms of anti-inflammatory action of erythromycin in human bronchial epithelial cells: possible role in the signaling pathway that regulates nuclear factor-kappaB activation. Antimicrob. Agents Chemother. 48, 1581-1585 (2004).
28. Li Y-J, Shimizu T, Hirata Y et al. EM, EM703 inhibit NF-kB activation induced by oxidative stress from diesel exhaust particle in human bronchial epithelial cells: importance in IL-8 transcription. Pulm. Pharmacol. Ther. 26(3), 1-7 (2013).
29. Li YJ, Azuma A, Usuki J et al. EM703 improves bleomycininduced pulmonary fibrosis in mice by the inhibition of TGF-β signaling in lung fibroblasts. Respir. Res. 7, 16 (2006).
30. Yu C, Azuma A, Li Y et al. EM703, a new derivative of erythromycin, inhibits transforming growth factor-beta signaling in human lung fibroblasts. Exp. Lung Res. 34, 343-354 (2008).
31. Ikeda H, Sunazuka T, Suzuki H et al. EM703, the new derivative of erythromycin, inhibits transcription of type I collagen in normal and scleroderma fibroblasts. J. Dermatol. Sci. 49(3), 195-205 (2008).
32. Sugawara A, Sueki A, Hirose T et al. Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents. Bioorg. Med. Chem. Lett. 21(11), 3373-3376 (2011).
33. Sugawara A, Sueki A, Hirose T et al. Novel 12-membered non-antibiotic macrolides, EM900 series with antiinflammatory and/or immunomodulatory activity; synthesis, structure-activity relationships and in vivo study. J. Antibiot. (Tokyo) 65(9), 487-490 (2012).
34. Bauer J, Vine M, Cori I et al. Impact of stereochemistry on the biological activity of novel oleandomycin derivatives. Bioorg. Med. Chem. 20(7), 2274-2281 (2012).
35. Kudoh S, Keicho N. Diffuse panbronchiolitis. Clin. Chest Med. 33(2), 297-305 (2012).
36. Nguyen M, Chung EP. Telithromycin: the first ketolide antimicrobial. Clin. Ther. 27(8), 1144-1163 (2005).
37. Brinker AD, Wassel RT, Lyndly J et al. Telithromycinassociated hepatotoxicity: Clinical spectrum and causality assessment of 42 cases. Hepatology 49(1), 250-257 (2009).
38. Bertrand D, Bertrand S, Neveu E, Fernandes P. Molecular characterization of off-target activities of telithromycin: a potential role for nicotinic acetylcholine receptors. Antimicrob. Agents Chemother. 54, 5399-5402 (2010).
39. McGhee P, Clark C, Kosowska-Shick KM et al. et al. In vitro activity of CEM-101 against Streptococcus pneumoniae and Streptococcus pyogenes with defined macrolide resistance mechanisms. Antimicrob. Agents Chemother. 54(1), 230-238 (2010).
40. ClinicalTrials Database: NCT01756339. www.clinicaltrials.gov/show/ NCT01756339
41. ClinicalTrial Database: NCT01968733.www.clinicaltrials.gov/ct2/show/ NCT01968733
42. Kannan K, Mankin AS. Macrolide antibiotics in the ribosome exit tunnel: species-specific binding and action. Ann. NY Acad. Sci. 1241, 33-47 (2011).
43. Schlunzen F, Zarivach R, Harms J et al. Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature 413(6858), 814-821 (2001).
44. Schlunzen F, Harms JM, Franceschi F et al. Structural basis for the antibiotic activity of ketolides and azalides. Structure 11(3), 329-338 (2003).
45. Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA. The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol. Cell. 10(1), 117-128 (2002).
46. Novak P, Barber J, Cikos A et al. Free and bound state structures of 6-O-methyl homoerythromycins and epitope mapping of their interactions with ribosomes. Bioorg. Med. Chem. 17(16), 5857-5867 (2009).
47. Bulkley D, Innis CA, Blaha G, Steitz TA. Revisiting the structures of several antibiotics bound to the bacterial ribosome. Proc. Natl Acad. Sci. USA 107(40), 17158-17163 (2010).
48. Llano-Sotelo B, Dunkle J, Klepacki D et al. Binding and action of CEM-101, a new fluoroketolide antibiotic that inhibits protein synthesis. Antimicrob. Agents Chemother. 54(12), 4961-4970 (2010).
49. Berisio R, Harms J, Schluenzen F et al. Structural insight into the antibiotic action of telithromycin against resistant mutants. J. Bacteriol. 185, 4276-4279 (2003).
50. Felmingham D, Gruneberg RN. The Alexander Project 1996-1997: latest susceptibility data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections. J. Antimicrob. Chemother. 45, 191-203 (2000).
51. Jacobs MR, Felmingham D, Appelbaum PC, Gruneberg RN. The Alexander Project 1998-2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents. J. Antimicrob. Chemother. 52, 229-246 (2003).
52. Schito GC, Felmingham D. Susceptibility of Streptococcus pneumoniae to penicillin, azithromycin and telithromycin (PROTEKT 1999-2003). Int. J. Antimicrob. Agents. 26, 479-485 (2005).
53. Tramper-Stranders GA, Wolfs TFW, Fleer A, Kimpen JLL, Van Der Ent CK. Maintenance azithromycin treatment in pediatric patients with cystic fibrosis: long-term outcomes related to macrolide resistance and pulmonary function. Pediatr. Infect. Dis. J. 26, 8-12 (2007).
54. Phaff SJ, Tiddens HAWM, Verbrugh HA, Ott A. Macrolide resistance of Staphylococcus aureus and Haemophilus species associated with long-term azithromycin use in cystic fibrosis. J. Antimicrob. Chemother. 57, 741-746 (2006).
55. Altenburg J, De Graaff CS, van Der Werf TS, Boersma WG. Immunomodulatory effects of macrolide antibiotics-part 2: advantages and disadvantages of long-term, low-dose macrolide therapy. Respir. Int. Rev. Thorac. Dis. 81, 75-87 (2011).
56. Serisier DJ, Martin ML, Mcguckin MA et al. Effect of longterm, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis. JAMA309, 1260 (2013).
57. Albert RK, Connett J, Bailey WC et al. Azithromycin for prevention of exacerbation of COPD. N. Engl. J. Med.365, 689-698 (2011).
58. Brusselle GG, Vanderstichele C, Jordens P et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax 68(4), 322-329 (2013).
59. Gullberg E, Cao S, Berg OG et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 7(7), e1002158 (2011).
60. Goh E-B, Yim G, Tsui W, McClure J, Surette MG, Davies J. Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics. Proc. Natl Acad. Sci. USA 99(26), 17025-17030 (2002).
61. Yim G, Wang HH, Davies J. Antibiotics as signalling molecules. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 362(1483), 1195-1200 (2007).
62. Sommer MOA, Dantas G, Church GM. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 325(5944), 1128-1131 (2009).
63. Lutz L, Pereira DC, Paiva RM, Zavascki AP, Barth AL. Macrolides decrease the minimal inhibitory concentration of anti-pseudomonal agents against Pseudomonas aeruginosa from cystic fibrosis patients in biofilm. BMC Microbiol. 12, 196 (2012).
64. Vos R, Vanaudenaerde BM, Ottevaere A et al. Long-term azithromycin therapy for bronchiolitis obliterans syndrome: divide and conquer J. Heart Lung Transplant. 29(12), 1358-1368 (2010).
65. Gomez J, Banos V, Simarro E et al. Prospective, comparative study (1994-1998) of the influence of short-term prophylactic treatment with azithromycin on patients with advanced COPD. Rev. Esp. Quimioter. 13(4), 379-383 (2000).
66. Peters J, Anzueto A. Azithromycin once daily for 1 year reduced acute COPD exacerbations. Ann. Intern. Med. 156(2), JC1-JC10 (2012).
67. Blasi F, Bonardi D, Aliberti S et al. Long-term azithromycin use in patients with chronic obstructive pulmonary disease and tracheostomy. Pulm. Pharmacol. Ther. 23(3), 200-207 (2010).
68. He Z-Y, Ou L-M, Zhang J-Q et al. Effect of 6 months of erythromycin treatment on inflammatory cells in induced sputum and exacerbations in chronic obstructive pulmonary disease. Respiration 80(6), 445-452 (2010).
69. Hodge S, Hodge G, Jersmann H et al. Azithromycin improves macrophage phagocytic function and expression of mannose receptor in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 178(2), 139-148 (2008).
70. Hodge S, Reynolds PN. Low-dose azithromycin improves phagocytosis of bacteria by both alveolar and monocyte-derived macrophages in chronic obstructive pulmonary disease subjects. Respirology 17(5), 802-807 (2012).
71. Albert RK, Connett J, Curtis JL et al. Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis. 7, 767-777 (2012).
72. Uzun S, Djamin RS, Kluytmans J et al. Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS): study protocol for a randomised controlled trial. Trials 13, 82 (2012).
73. Reiter J, Demirel N, Mendy A ,Macrolides for the long-term management of asthma-a meta-analysis of randomized clinical trials. Allergy (68( 8), 1040-1049 ( 2013).
74. Mikailov A, Kane I, Aronoff SC, Luck R, Delvecchio MT. Utility of adjunctive macrolide therapy in treatment of children with asthma: a systematic review and meta-analysis. J. Asthma Allergy 6, 23-29 (2013).
75. Cameron EJ, Chaudhuri R, Mair F ,Randomized controlled trial of azithromycin in smokers with asthma. Eur. Respir. J. (42( 5), 1412-1415 (2013).
76. Shinkai M, Henke MO, Rubin BK. Macrolide antibiotics as immunomodulatory medications: proposed mechanisms of action. Pharmacol. Ther. 117, 393-405 (2008).
77. Ogrendik M, Karagoz N. Treatment of rheumatoid arthritis with roxithromycin: a randomized trial. Postgrad. Med. 123(5), 220-227 (2011).
78. Kanoh S, Rubin BK. Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin. Microbiol. Rev. 23, 590-615 (2010).
79. Tsai WC, Standiford TJ. Immunomodulatory effects of macrolides in the lung: lessons from in-vitro and in-vivo models. Curr. Pharm. Des. 10, 3081-3093 (2004).
80. Altenburg J, de Graaff CS, van der Werf TS, Boersma WG. Immunomodulatory effects of macrolide antibiotics-part 1: biological mechanisms. Respiration 81(1), 67-74 (2011).
81. Culi O, Erakovi V, Parnham MJ. Anti-inflammatory effects of macrolide antibiotics. Eur. J. Pharmacol. 429(1-3), 209-229 (2001).
82. Leiva M, Ruiz-Bravo A, Jimenez-Valera M. Effects of telithromycin in invitro and invivo models of lipopolysaccharide-induced airway inflammation. Chest 134, 20-29 (2008).
83. Leiva M, Ruiz-Bravo A, Moreno E, Jimenez-Valera M. The anti-inflammatory activity of telithromycin in a mouse model of septic shock. Int. J. Antimicrob. Agents. 29(3), 364-365 (2007).
84. Lotter K, Hocherl K, Bucher M, Kees F. Invivo efficacy of telithromycin on cytokine and nitric oxide formation in lipopolysaccharide-induced acute systemic inflammation in mice. J. Antimicrob. Chemother. 58, 615-621 (2006).
85. Kobayashi Y, Wada H, Rossios C et al. A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition. J. Pharmacol. Exp. Ther. 345(1), 76-84 (2013).
86. Culi O, Erakovi V, Cepelak I et al. Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects. Eur. J. Pharmacol. 450(3), 277-289 (2002).
87. Shinkai M, Lopez-Boado YS, Rubin BK. Clarithromycin has an immunomodulatory effect on ERK-mediated inflammation induced by Pseudomonas aeruginosa flagellin. J. Antimicrob. Chemother. 59, 1096-1101 (2007).
88. Shinkai M, Foster GH, Rubin BK. Macrolide antibiotics modulate ERK phosphorylation and IL-8 and GM-CSF production by human bronchial epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L75-L85 (2006).
89. Tkalevi VI, Hrvai B, Pašali I, Erakovi Haber V, Glojnari I. Immunomodulatory effects of azithromycin on serum amyloid A production in lipopolysaccharide-induced endotoxemia in mice. J. Antibiot. (Tokyo) 64(7), 515-517 (2011).
90. Kim IJ, Kim H, Or YS, Wang G: US20090209547 (2009).
91. Enanta Pharmaceuticals Inc.: WO2010096051 (2010).
92. Enanta Pharmaceuticals Inc.: WO2008014221 (2008).
93. PLIVA Inc.: US6369035 (2002).
94. GlaxoSmithKline Research Centre Zagreb d.o.o.: WO2010086350 (2010).
95. Rib-X Pharmaceuticals Inc.: WO2008143729 (2009).
96. Rib-X Pharmaceuticals Inc.: WO2008106224 (2008).
97. Ištuk ZM, Cikoš A, Gembarovski D et al. Novel 9a,11-bridged azalides: One-pot synthesis of Ń-substituted 2-imino-1,3-oxazolidines condensed to an azalide aglycone. Bioorg. Med. Chem. 19, 556-566 (2011).
98. Maruši Ištuk Z, Vujasinovi I, ikoš A, Kragol G. Regioselective 2-imino-1,3-thiazolidine vs. 2-imino-1,3-oxazolidine formation from the vicinal sec-amino alcohol of desosamine. Eur. J. Org. Chem. 2013(21), 4666-4673 (2013).
99. Jakopovi IP, Krajai MB, Skugor MM et al. Novel desosamine-modified 14-and 15-membered macrolides without antibacterial activity. Bioorg. Med. Chem. Lett. 22(10), 3527-3530 (2012).
100. Catabasis Pharmaceuticals Inc.: WO2011116312 (2011).
101. PLIVA Inc.: EP0283055 (1989).
102. Valosin containing protein (VCP) interacts with macrolide antibiotics without mediating their anti-inflammatory activitiesEur. J. Pharmacol.6771- 31631722012
103. Morimura T, Hashiba M, Kameda H et al. Identification of macrolide antibiotic-binding Human-p8 protein. J. Antibiot. (Tokyo) 61(5), 291-296 (2008).
104. Morimura T, Noda N, Kato Y et al. Identification of antibiotic clarithromycin binding peptide displayed by T7 phage particles. J. Antibiot. (Tokyo) 59(10), 625-632 (2006).
105. Yamanaka Y, Tamari M, Nakahata T, Nakamura Y. Gene expression profiles of human small airway epithelial cells treated with low doses of 14-and 16-membered macrolides. Biochem. Biophys. Res. Commun. 287(1), 198-203 (2001).
106. Van Bambeke F, Montenez JP, Piret J, Tulkens PM, Courtoy PJ, Mingeot-Leclercq MP. Interaction of the macrolide azithromycin with phospholipids. I. Inhibition of lysosomal phospholipase A1 activity. Eur. J. Pharmacol. 314(1-2), 203-214 (1996).
107. Montenez JP, Van Bambeke F, Piret J et al. Interaction of the macrolide azithromycin with phospholipids. II. Biophysical and computer-aided conformational studies. Eur. J. Pharmacol. 314(1-2), 215-227 (1996).
108. Tyteca D, Van Der Smissen P, Van Bambeke F et al. Azithromycin, a lysosomotropic antibiotic, impairs fluidphase pinocytosis in cultured fibroblasts. Eur. J. Cell Biol. 80(7), 466-478 (2001).
109. Muni V, Banjanac M, Koštrun S et al. Intensity of macrolide anti-inflammatory activity in J774A.1 cells positively correlates with cellular accumulation and phospholipidosis. Pharmacol. Res. 64(3), 298-307 (2011).
110. Banjanac M, Muni Kos V, Nuji K et al. Anti-inflammatory mechanism of action of azithromycin in LPS-stimulated J774A.1 cells. Pharmacol. Res. 66(4), 357-362 (2012).
111. Nuji K, Banjanac M, Muni V, Polanec D, Erakovi Haber V. Impairment of lysosomal functions by azithromycin and chloroquine contributes to anti-inflammatory phenotype. Cell. Immunol. 279(1), 78-86 (2012).
112. Vrani M, Banjanac M, Nuji K et al. Azithromycin distinctively modulates classical activation of human monocytes in vitro. Br. J. Pharmacol. 165(5), 1348-1360 (2012).
113. Polancec DS, Munic Kos V, Banjanac M et al. Azithromycin drives in vitro GM-CSF/IL-4-induced differentiation of human blood monocytes toward dendritic-like cells with regulatory properties. J. Leukoc. Biol. 91(2), 229-243 (2012).
114. Smith DA, Di L, Kerns EH. The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery. Nat. Rev. Drug Discov. 9(12), 929-939 (2010).