Login Register Cart 0
Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis and Antibacterial Activity of Erythromycin 9-Acylhydrazone Derivates

Author(s): Zhiling Cao*, Wei Zheng, Maolong Huang, Xinran Yao, Wenrong Zhu, Lanjun Sheng, Zaixiu Pan, Yuzong Bian, Tian Zhang and Cong Zhu

Volume 19, Issue 6, 2023

Published on: 30 January, 2023

Page: [586 - 593] Pages: 8

DOI: 10.2174/1573406419666230103145209

Price: $65

Abstract

Background: Some species of Marine bacteria pose great risks to human and mariculture organisms. Meanwhile, Vibrio harveyi and Vibrio parahaemolyticus strains have acquired resistance to many antibiotics.

Objective: A novel series of erythromycin 9-acylhydrazone derivatives were synthesized and evaluated for their in vitro antibacterial activity against marine pathogens.

Methods: The site-selective N-acylation of erythromycin hydrazone was achieved using acid chloride/ triethylamine in methanol as the reaction system. All the synthesized target compounds were evaluated for their antibacterial activity by determination of minimum inhibitory concentrations (MICs) using the broth microdilution method.

Results: All the tested acylhydrazone compounds showed moderate to high activity with MIC value 0.125-1 μg/mL against Vibrio parahaemolyticus and Vibrio harveyi.

Conclusion: The introduction of the acylhydrazone moiety at the C-9 position of erythromycin improved its activity against the above-mentioned marine bacteria strains.

« Previous Next »
Graphical Abstract

[1]
Zhang, X.H.; He, X.; Austin, B. Vibrio harveyi: A serious pathogen of fish and invertebrates in mariculture. Mar. Life Sci. Technol., 2020, 2(3), 231-245.
[http://dx.doi.org/10.1007/s42995-020-00037-z] [PMID: 32419972]
[2]
Ghenem, L.; Elhadi, N.; Alzahrani, F.; Nishibuchi, M. Vibrio Parahaemolyticus: A review on distribution, pathogenesis, virulence determinants and epidemiology. Saudi J. Med. Med. Sci., 2017, 5(2), 93-103.
[http://dx.doi.org/10.4103/sjmms.sjmms_30_17] [PMID: 30787765]
[3]
Finkelstein, R.; Oren, I. Soft tissue infections caused by marine bacterial pathogens: epidemiology, diagnosis, and management. Curr. Infect. Dis. Rep., 2011, 13(5), 470-477.
[http://dx.doi.org/10.1007/s11908-011-0199-3] [PMID: 21785929]
[4]
Tena, D.; Arias, M.; Álvarez, B.T.; Mauleón, C.; Jiménez, M.P.; Bisquert, J. Fulminant necrotizing fasciitis due to Vibrio parahaemolyticus. J. Med. Microbiol., 2010, 59(2), 235-238.
[http://dx.doi.org/10.1099/jmm.0.014654-0] [PMID: 19797463]
[5]
Su, Y.C.; Liu, C. Vibrio parahaemolyticus: A concern of seafood safety. Food Microbiol., 2007, 24(6), 549-558.
[http://dx.doi.org/10.1016/j.fm.2007.01.005] [PMID: 17418305]
[6]
Broberg, C.A.; Calder, T.J.; Orth, K. Vibrio parahaemolyticus cell biology and pathogenicity determinants. Microbes Infect., 2011, 13(12-13), 992-1001.
[http://dx.doi.org/10.1016/j.micinf.2011.06.013] [PMID: 21782964]
[7]
Mok, J.S.; Cho, S.R.; Park, Y.J.; Jo, M.R.; Ha, K.S.; Kim, P.H.; Kim, M.J. Distribution and antimicrobial resistance of Vibrio parahaemolyticus isolated from fish and shrimp aquaculture farms along the Korean coast. Mar. Pollut. Bull., 2021, 171, 112785.
[http://dx.doi.org/10.1016/j.marpolbul.2021.112785] [PMID: 34340145]
[8]
Silvester, R.; Alexander, D.; Ammanamveetil, M.H.A. Prevalence, antibiotic resistance, virulence and plasmid profiles of Vibrio parahaemolyticus from a tropical estuary and adjoining traditional prawn farm along the southwest coast of India. Ann. Microbiol., 2015, 65(4), 2141-2149.
[http://dx.doi.org/10.1007/s13213-015-1053-x]
[9]
Baker-Austin, C.; Stockley, L.; Rangdale, R.; Martinez-Urtaza, J. Environmental occurrence and clinical impact of Vibrio vulnificus and Vibrio parahaemolyticus: a European perspective. Environ. Microbiol. Rep., 2010, 2(1), 7-18.
[http://dx.doi.org/10.1111/j.1758-2229.2009.00096.x] [PMID: 23765993]
[10]
Choi, M.; Stevens, A.M.; Smith, S.A.; Taylor, D.P.; Kuhn, D.D. Strain and dose infectivity of Vibrio parahaemolyticus: the causative agent of early mortality syndrome in shrimp. Aquacult. Res., 2017, 48(7), 3719-3727.
[http://dx.doi.org/10.1111/are.13197]
[11]
Loo, K.Y.; Letchumanan, V.; Law, J.W.F.; Pusparajah, P.; Goh, B.H.; Ab Mutalib, N.S.; He, Y.W.; Lee, L.H. Incidence of antibiotic resistance in Vibrio spp. Rev. Aquacult., 2020, 12(4), 2590-2608.
[http://dx.doi.org/10.1111/raq.12460]
[12]
Douthwaite, S. Structure–activity relationships of ketolides vs. macrolides. Clin. Microbiol. Infect., 2001, 7(Suppl. 3), 11-17.
[http://dx.doi.org/10.1046/j.1469-0691.2001.0070s3011.x] [PMID: 11523556]
[13]
Zhanel, G.G.; Dueck, M.; Hoban, D.J.; Vercaigne, L.M.; Embil, J.M.; Gin, A.S.; Karlowsky, J.A. Review of macrolides and ketolides: focus on respiratory tract infections. Drugs, 2001, 61(4), 443-498.
[http://dx.doi.org/10.2165/00003495-200161040-00003] [PMID: 11324679]
[14]
Thota, S.; Rodrigues, D.A.; Pinheiro, P.S.M.; Lima, L.M.; Fraga, C.A.M.; Barreiro, E.J. N-Acylhydrazones as drugs. Bioorg. Med. Chem. Lett., 2018, 28(17), 2797-2806.
[http://dx.doi.org/10.1016/j.bmcl.2018.07.015] [PMID: 30006065]
[15]
Wang, X.L.; Zhang, Y.B.; Tang, J.F.; Yang, Y.S.; Chen, R.Q.; Zhang, F.; Zhu, H.L. Design, synthesis and antibacterial activities of vanillic acylhydrazone derivatives as potential β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors. Eur. J. Med. Chem., 2012, 57, 373-382.
[http://dx.doi.org/10.1016/j.ejmech.2012.09.009] [PMID: 23124163]
[16]
Rozada, A.M.F.; Rodrigues-Vendramini, F.A.V.; Gonçalves, D.S.; Rosa, F.A.; Basso, E.A.; Seixas, F.A.V.; Kioshima, É.S.; Gauze, G.F. Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones. Bioorg. Med. Chem. Lett., 2020, 30(14), 127244.
[http://dx.doi.org/10.1016/j.bmcl.2020.127244] [PMID: 32527546]
[17]
Carcelli, M.; Rogolino, D.; Gatti, A.; De Luca, L.; Sechi, M.; Kumar, G.; White, S.W.; Stevaert, A.; Naesens, L. N-acylhydrazone inhibitors of influenza virus PA endonuclease with versatile metal binding modes. Sci. Rep., 2016, 6(1), 31500.
[http://dx.doi.org/10.1038/srep31500] [PMID: 27510745]
[18]
Huttner, A.; Stewardson, A. Nitrofurans: nitrofurazone, furazidine, and nitrofurantoin. In:Kucers’ The Use of Antibiotics; CRC Press, 2017, pp. 1784-1798.
[19]
Shao, Z.B.; Jiang, K.J.; Cao, L.G.; Chao, C.; Wu, Y.Y.; Su, Z.Q.; Wang, Y.X.; Liu, S.H.; Wu, Y.R.; Liu, W.W. Synthesis of emodin acylhydrazone derivatives and determination of Vibrio harveyi inhibitory activity. Chem. Nat. Compd., 2022, 58(2), 222-226.
[http://dx.doi.org/10.1007/s10600-022-03645-6]
[20]
Dinos, G.P. The macrolide antibiotic renaissance. Br. J. Pharmacol., 2017, 174(18), 2967-2983.
[http://dx.doi.org/10.1111/bph.13936] [PMID: 28664582]
[21]
Zhao, Z.; Zhang, X.; Jin, L.; Yang, S.; Lei, P. Synthesis and antibacterial activity of novel ketolides with 11,12-quinoylalkyl side chains. Bioorg. Med. Chem. Lett., 2018, 28(14), 2358-2363.
[http://dx.doi.org/10.1016/j.bmcl.2018.06.039] [PMID: 29937059]
[22]
Fernandes, P.; Pereira, D.; Watkins, P.B.; Bertrand, D. Differentiating the pharmacodynamics and toxicology of macrolide and ketolide antibiotics. J. Med. Chem., 2020, 63(12), 6462-6473.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01159] [PMID: 31644280]
[23]
Fan, B.Z.; Hiasa, H.; Lv, W.; Brody, S.; Yang, Z.Y.; Aldrich, C.; Cushman, M.; Liang, J.H. Design, synthesis and structure-activity relationships of novel 15-membered macrolides: Quinolone/quinoline-containing sidechains tethered to the C-6 position of azithromycin acylides. Eur. J. Med. Chem., 2020, 193, 112222.
[http://dx.doi.org/10.1016/j.ejmech.2020.112222] [PMID: 32200200]
[24]
Janas, A.; Przybylski, P. 14- and 15-membered lactone macrolides and their analogues and hybrids: structure, molecular mechanism of action and biological activity. Eur. J. Med. Chem., 2019, 182, 111662.
[http://dx.doi.org/10.1016/j.ejmech.2019.111662] [PMID: 31499358]
[25]
Nguyen, H.L.; An, P.H.; Thai, N.Q.; Linh, H.Q.; Li, M.S. Erythromycin, Cethromycin and Solithromycin display similar binding affinities to the E. coli’s ribosome: A molecular simulation study. J. Mol. Graph. Model., 2019, 91, 80-90.
[http://dx.doi.org/10.1016/j.jmgm.2019.06.002] [PMID: 31200217]
[26]
Liang, J.H.; Han, X. Structure-activity relationships and mechanism of action of macrolides derived from erythromycin as antibacterial agents. Curr. Top. Med. Chem., 2013, 13(24), 3131-3164.
[http://dx.doi.org/10.2174/15680266113136660223] [PMID: 24200358]
[27]
Wikler, M.A. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved Standard, 8th ed; Clinical and Laboratory Standards Institute, 2009, p. 29.
[28]
Congiu, C.; Onnis, V. Synthesis and biological evaluation of novel acylhydrazone derivatives as potential antitumor agents. Bioorg. Med. Chem., 2013, 21(21), 6592-6599.
[http://dx.doi.org/10.1016/j.bmc.2013.08.026] [PMID: 24071449]
[29]
Attanasi, O.A.; Santeusanio, S.; Serra-Zanetti, F. Treatment of conjugated azoalkenes with N-acyl-N’-tosylhydrazides. A useful entry to asymmetric bis-acylhydrazones. Org. Prep. Proced. Int., 1994, 26(4), 485-488.
[http://dx.doi.org/10.1080/00304949409458044]
[30]
Rodríguez-Argüelles, M.C.; Cao, R.; García-Deibe, A.M.; Pelizzi, C.; Sanmartín-Matalobos, J.; Zani, F. Antibacterial and antifungal activity of metal(II) complexes of acylhydrazones of 3-isatin and 3-(N-methyl)isatin. Polyhedron, 2009, 28(11), 2187-2195.
[http://dx.doi.org/10.1016/j.poly.2008.12.038]
[31]
Arenz, S.; Ramu, H.; Gupta, P.; Berninghausen, O.; Beckmann, R.; Vázquez-Laslop, N.; Mankin, A.S.; Wilson, D.N. Molecular basis for erythromycin-dependent ribosome stalling during translation of the ErmBL leader peptide. Nat. Commun., 2014, 5(1), 3501.
[http://dx.doi.org/10.1038/ncomms4501] [PMID: 24662426]
[32]
Katz, L.; Ashley, G.W. Translation and protein synthesis: macrolides. Chem. Rev., 2005, 105(2), 499-528.
[http://dx.doi.org/10.1021/cr030107f] [PMID: 15700954]
[33]
Fernandes, P.; Martens, E.; Bertrand, D.; Pereira, D. The solithromycin journey—It is all in the chemistry. Bioorg. Med. Chem., 2016, 24(24), 6420-6428.
[http://dx.doi.org/10.1016/j.bmc.2016.08.035] [PMID: 27595539]
[34]
Ackermann, G.; Rodloff, A.C. Drugs of the 21st century: Telithromycin (HMR 3647) the first ketolide. J. Antimicrob. Chemother., 2003, 51(3), 497-511.
[http://dx.doi.org/10.1093/jac/dkg123] [PMID: 12615850]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy