Efficient Synthesis and Antibacterial Profile of Bis(2-hydroxynaphthalene- 1,4-dione)

Author(s): Juliana S. Novais, Aline C. Rosandiski, Carolina M. de Carvalho, Letícia S. de Saules Silva, Lais C. dos S. Velasco de Souza, Marcos V. Santana, Nathalia R.C. Martins, Helena C. Castro, Vitor F. Ferreira, Daniel T.G. Gonzaga, Gabriel O. de Resende*, Fernando de C. da Silva*

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 2 , 2020

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Graphical Abstract:


Abstract:

Background: Antibacterial resistance is a serious public health problem infecting millions in the global population. Currently, there are few antimicrobials on the market against resistant bacterial infections. Therefore, there is an urgent need for new therapeutic options against these strains.

Objective: In this study, we synthesized and evaluated ten Bis(2-hydroxynaphthalene-1,4-dione) against Gram-positive strains, including a hospital Methicillin-resistant (MRSA), and Gram-negative strains.

Methods: The compounds were prepared by condensation of aldehydes and lawsone in the presence of different L-aminoacids as catalysts in very good yields. The compounds were submitted to antibacterial analysis through disk diffusion and Minimal Inhibitory Concentration (MIC) assays.

Results: L-aminoacids have been shown to be efficient catalysts in the preparation of Bis(2- hydroxynaphthalene-1,4-dione) from 2-hydroxy-1,4-naphthoquinones and arylaldehydes in excellent yields of up to 96%. The evaluation of the antibacterial profile against Gram-positive strains (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228) also including a hospital Methicillin-resistant S. aureus (MRSA) and Gram-negative strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Klebsiella pneumoniae ATCC 4352), revealed that seven compounds showed antibacterial activity within the Clinical and Laboratory Standards Institute (CLSI) levels mainly against P. aeruginosa ATCC 27853 (MIC 8-128 µg/mL) and MRSA (MIC 32-128 µg/mL). In addition, the in vitro toxicity showed all derivatives with no hemolytic effects on healthy human erythrocytes. Furthermore, the derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) parameters, and a similar profile to antibiotics currently in use. Finally, the in silico evaluation pointed to a structure-activity relationship related to lipophilicity for these compounds. This feature may help them in acting against Gram-negative strains, which present a rich lipid cell wall selective for several antibiotics.

Conclusion: Our data showed the potential of this series for exploring new and more effective antibacterial activities in vivo against other resistant bacteria.

Keywords: Bacterial resistance, Naphthoquinone, Lawsone, Antimicrobials, Gram-positive, Gram-negative, In silico study.

[1]
Trotter, A.J.; Aydin, A.; Strinden, M.J.; O’Grady, J. Recent and emerging technologies for the rapid diagnosis of infection and antimicrobial resistance. Curr. Opin. Microbiol., 2019, 51, 39-45.
[http://dx.doi.org/10.1016/j.mib.2019.03.001] [PMID: 31077935]
[2]
McAdams, D.; Wollein Waldetoft, K.; Tedijanto, C.; Lipsitch, M.; Brown, S.P. Resistance diagnostics as a public health tool to combat antibiotic resistance: A model-based evaluation. PLoS Biol., 2019, 17(5) e3000250
[http://dx.doi.org/10.1371/journal.pbio.3000250] [PMID: 31095567]
[3]
Tacconelli, E.; Carrara, E.; Savoldi, A.; Harbarth, S.; Mendelson, M.; Monnet, D.L.; Pulcini, C.; Kahlmeter, G.; Kluytmans, J.; Carmeli, Y.; Ouellette, M.; Outterson, K.; Patel, J.; Cavaleri, M.; Cox, E.M.; Houchens, C.R.; Grayson, M.L.; Hansen, P.; Singh, N.; Theuretzbacher, U.; Magrini, N. WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis., 2018, 18(3), 318-327.
[http://dx.doi.org/10.1016/S1473-3099(17)30753-3] [PMID: 29276051]
[4]
World Health Organization Prioritization of pathogens to guide discovery, research and development of new antibiotics for drugresistant bacterial infections, including tuberculosis, 2017. Available at:. http://www.who.int/medicines/areas/rational_use/prioritization-of-pathogens/en/ (Accessed May 29, 2018).
[5]
López-Causapé, C.; Cabot, G.; Del Barrio-Tofiño, E.; Oliver, A. The Versatile Mutational Resistome of Pseudomonas aeruginosa. Front. Microbiol., 2018, 9, 685.
[http://dx.doi.org/10.3389/fmicb.2018.00685] [PMID: 29681898]
[6]
Lee, A.S.; de Lencastre, H.; Garau, J.; Kluytmans, J.; Malhotra-Kumar, S.; Peschel, A.; Harbarth, S. Methicillin-resistant Staphylococcus aureus. Nat. Rev. Dis. Primers, 2018, 4, 18033.
[http://dx.doi.org/10.1038/nrdp.2018.33] [PMID: 29849094]
[7]
Bengtsson-Palme, J.; Kristiansson, E.; Larsson, D.G.J. Environmental factors influencing the development and spread of antibiotic resistance. FEMS Microbiol. Rev., 2018, 42(1), 68-80.
[http://dx.doi.org/10.1093/femsre/fux053] [PMID: 29069382]
[8]
da Silva, F.C.; Ferreira, V.F. Natural naphthoquinones with great importance in medicinal chemistry. Curr. Org. Synth., 2016, 13, 334-371.
[http://dx.doi.org/10.2174/1570179412666150817220343]
[9]
Collins, M.D.; Jones, D. Distribution of isoprenoid quinone structural types in bacteria and their taxonomic implication. Microbiol. Rev., 1981, 45(2), 316-354.
[PMID: 7022156]
[10]
Bader, M.; Muse, W.; Ballou, D.P.; Gassner, C.; Bardwell, J.C.A. Oxidative protein folding is driven by the electron transport system. Cell, 1999, 98(2), 217-227.
[http://dx.doi.org/10.1016/S0092-8674(00)81016-8] [PMID: 10428033]
[11]
Sakuragi, Y.; Zybailov, B.; Shen, G.; Jones, A.D.; Chitnis, P.R.; van der Est, A.; Bittl, R.; Zech, S.; Stehlik, D.; Golbeck, J.H.; Bryant, D.A. Insertional inactivation of the menG gene, encoding 2-phytyl-1,4-naphthoquinone methyltransferase of Synechocystis sp. PCC 6803, results in the incorporation of 2-phytyl-1,4-naphthoquinone into the A(1) site and alteration of the equilibrium constant between A(1) and F(X) in photosystem I. Biochemistry, 2002, 41(1), 394-405.
[http://dx.doi.org/10.1021/bi011297w] [PMID: 11772039]
[12]
Ferreira, S.B.; Gonzaga, D.T.G.; Santos, W.C.; Araújo, K.G.L.; Ferreira, V.F. β-Lapachona: Sua Importância em Química Medicinal e Modificações Estruturais. Rev. Virtual Quim., 2010, 2, 140-160.
[13]
Lara, L.S.; Moreira, C.S.; Calvet, C.M.; Lechuga, G.C.; Souza, R.S.; Bourguignon, S.C.; Ferreira, V.F.; Rocha, D.; Pereira, M.C.S. Efficacy of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphtho-quinone derivatives against different Trypanosoma cruzi discrete type units: Identification of a promising hit compound. Eur. J. Med. Chem., 2018, 144, 572-581.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.052] [PMID: 29289882]
[14]
Camara, C.A.; Silva, T.M.; da-Silva, T.G.; Martins, R.M.; Barbosa, T.P.; Pinto, A.C.; Vargas, M.D. Molluscicidal activity of 2-hydroxy-[1,4]naphthoquinone and derivatives. An. Acad. Bras. Cienc., 2008, 80(2), 329-334.
[http://dx.doi.org/10.1590/S0001-37652008000200011] [PMID: 18506259]
[15]
Futuro, D.O.; Ferreira, P.G.; Nicoletti, C.D.; Borba-Santos, L.P.; Silva, F.C.D.; Rozental, S.; Ferreira, V.F. The antifungal activity of naphthoquinones: An integrative review. An. Acad. Bras. Cienc., 2018, 90(1)(Suppl. 2), 1187-1214.
[http://dx.doi.org/10.1590/0001-3765201820170815] [PMID: 29873671]
[16]
Garcia Ferreira, P.; Pereira Borba-Santos, L.; Noronha, L.L.; Deckman Nicoletti, C.; de Sá Haddad Queiroz, M.; de Carvalho da Silva, F.; Rozental, S.; Omena Futuro, D.; Francisco Ferreira, V. Synthesis, stability studies, and antifungal evaluation of substituted α- and β-2,3-dihydrofuranaphthoquinones against Sporothrix brasiliensis and Sporothrix schenckii. Molecules, 2019, 24(5), 930-944.
[http://dx.doi.org/10.3390/molecules24050930] [PMID: 30866442]
[17]
Janeczko, M.; Kubiński, K.; Martyna, A.; Muzyczka, A.; Boguszewska-Czubara, A.; Czernik, S.; Tokarska-Rodak, M.; Chwedczuk, M.; Demchuk, O.M.; Golczyk, H.; Masłyk, M. 1,4-Naphthoquinone derivatives potently suppress Candida albicans growth, inhibit formation of hyphae and show no toxicity toward zebrafish embryos. J. Med. Microbiol., 2018, 67(4), 598-609.
[http://dx.doi.org/10.1099/jmm.0.000700] [PMID: 29461185]
[18]
Costa, D.C.S.; de Almeida, G.S.; Rabelo, V.W-H.; Cabral, L.M.; Sathler, P.C.; Alvarez Abreu, P.; Ferreira, V.F.; Cláudio Rodrigues Pereira da Silva, L.; da Silva, F.C. Synthesis and evaluation of the cytotoxic activity of Furanaphthoquinones tethered to 1H-1,2,3-triazoles in Caco-2, Calu-3, MDA-MB231 cells. Eur. J. Med. Chem., 2018, 156, 524-533.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.018] [PMID: 30025347]
[19]
de Paiva, Y.G.; Silva, T.L.; Xavier, A.F.A.; Cardoso, M.F.C.; da Silva, F.C.; Silva, M.F.S.; Pinheiro, D.P.; Pessoa, C.; Ferreira, V.F.; Goulart, M.O.F. relationship between electrochemical parameters, cytotoxicity data against cancer cells of 3-thio-substituted nor-beta-lapachone derivatives. implications for cancer therapy. J. Braz. Chem. Soc., 2019, 30, 658-672.
[http://dx.doi.org/10.21577/0103-5053.20180248]
[20]
Bortolot, C.S. da S M Forezi, L.; Marra, R.K.F.; Reis, M.I.P.; Sá, B.V.F.E.; Filho, R.I.; Ghasemishahrestani, Z.; Sola-Penna, M.; Zancan, P.; Ferreira, V.F.; de C da Silva, F. Design, synthesis and biological evaluation of 1h-1,2,3-triazole-linked-1h-dibenzo[b,h]xanthenes as inductors of ros-mediated apoptosis in the breast cancer cell line MCF-7. Med. Chem., 2019, 15(2), 119-129.
[http://dx.doi.org/10.2174/1573406414666180524071409] [PMID: 29792156]
[21]
Manickam, M.; Boggu, P.R.; Cho, J.; Nam, Y.J.; Lee, S.J.; Jung, S.H. Investigation of chemical reactivity of 2-alkoxy-1,4-naphthoquinones and their anticancer activity. Bioorg. Med. Chem. Lett., 2018, 28(11), 2023-2028.
[http://dx.doi.org/10.1016/j.bmcl.2018.04.060] [PMID: 29735338]
[22]
Ribeiro, K.A.; de Carvalho, C.M.; Molina, M.T.; Lima, E.P.; López-Montero, E.; Reys, J.R.; de Oliveira, M.B.; Pinto, A.V.; Santana, A.E.; Goulart, M.O. Activities of naphthoquinones against Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae), vector of dengue and Biomphalaria glabrata (Say, 1818), intermediate host of Schistosoma mansoni. Acta Trop., 2009, 111(1), 44-50.
[http://dx.doi.org/10.1016/j.actatropica.2009.02.008] [PMID: 19426662]
[23]
Taka, E.; Mazzio, E.A.; Goodman, C.B.; Redmon, N.; Flores-Rozas, H.; Reams, R.; Darling-Reed, S.; Soliman, K.F. Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells. J. Neuroimmunol., 2015, 286, 5-12.
[http://dx.doi.org/10.1016/j.jneuroim.2015.06.011] [PMID: 26298318]
[24]
Brandão, G.C.; Rocha Missias, F.C.; Arantes, L.M.; Soares, L.F.; Roy, K.K.; Doerksen, R.J.; Braga de Oliveira, A.; Pereira, G.R. Antimalarial naphthoquinones. Synthesis via click chemistry, in vitro activity, docking to PfDHODH and SAR of lapachol-based compounds. Eur. J. Med. Chem., 2018, 145, 191-205.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.051] [PMID: 29324340]
[25]
Gonzaga, D.T.G.; Gomes, R.S.P.; Marra, R.K.F.; da Silva, F.C.; Gomes, M.W.L.; Ferreira, D.F.; Santos, R.M.A.; Pinto, A.M.V.; Ratcliffe, N.A.; Cirne-Santos, C.C.; Barros, C.S.; Ferreira, V.F.; Paixão, I.C.N.P. Inhibition of Zika Virus Replication by Synthetic Bis-Naphthoquinones. J. Braz. Chem. Soc., 2019, 30, 1697-1706.
[http://dx.doi.org/10.21577/0103-5053.20190071]
[26]
da Costa, E.C.; Amorim, R.; da Silva, F.C.; Rocha, D.R.; Papa, M.P.; de Arruda, L.B.; Mohana-Borges, R.; Ferreira, V.F.; Tanuri, A.; da Costa, L.J.; Ferreira, S.B. Synthetic 1,4-pyran naphthoquinones are potent inhibitors of dengue virus replication. PLoS One, 2013, 8(12) e82504
[http://dx.doi.org/10.1371/journal.pone.0082504] [PMID: 24376541]
[27]
Novais, J.S.; Moreira, C.S.; Silva, A.C.J.A.; Loureiro, R.S.; Sá Figueiredo, A.M.; Ferreira, V.F.; Castro, H.C.; da Rocha, D.R. Antibacterial naphthoquinone derivatives targeting resistant strain Gram-negative bacteria in biofilms. Microb. Pathog., 2018, 118, 105-114.
[http://dx.doi.org/10.1016/j.micpath.2018.03.024] [PMID: 29550501]
[28]
Gong, X.; Gutala, R.; Jaiswal, A.K. Quinone oxidoreductases and vitamin K metabolism. Vitam. Horm., 2008, 78, 85-101.
[http://dx.doi.org/10.1016/S0083-6729(07)00005-2] [PMID: 18374191]
[29]
Cruz-Muñiz, M.Y.; López-Jacome, L.E.; Hernández-Durán, M.; Franco-Cendejas, R.; Licona-Limón, P.; Ramos-Balderas, J.L.; Martinéz-Vázquez, M.; Belmont-Díaz, J.A.; Wood, T.K.; García-Contreras, R. Repurposing the anticancer drug mitomycin C for the treatment of persistent Acinetobacter baumannii infections. Int. J. Antimicrob. Agents, 2017, 49(1), 88-92.
[http://dx.doi.org/10.1016/j.ijantimicag.2016.08.022] [PMID: 27939675]
[30]
Jasra, S.; Anampa, J. Anthracycline use for early stage breast cancer in the modern era: A review. Curr. Treat. Options Oncol., 2018, 19(6), 30.
[http://dx.doi.org/10.1007/s11864-018-0547-8] [PMID: 29752560]
[31]
Gao, X.; Liu, X.; Shan, W.; Liu, Q.; Wang, C.; Zheng, J.; Yao, H.; Tang, R.; Zheng, J. Anti-malarial atovaquone exhibits anti-tumor effects by inducing DNA damage in hepatocellular carcinoma. Am. J. Cancer Res., 2018, 8(9), 1697-1711.
[PMID: 30323964]
[32]
Smith, L.; Serrano, D.R.; Mauger, M.; Bolás-Fernández, F.; Dea-Ayuela, M.A.; Lalatsa, A. Orally bioavailable and effective buparvaquone lipid-based nanomedicines for visceral leishmaniasis. Mol. Pharm., 2018, 15(7), 2570-2583.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00097] [PMID: 29762040]
[33]
Jordão, A.K.; Vargas, M.D.; Pinto, A.C.; da Silva, F.C.; Ferreira, V.F. Lawsone in organic synthesis. RSC Advances, 2015, 5, 67909-67943.
[http://dx.doi.org/10.1039/C5RA12785H]
[34]
Cardoso, M.F.C.; Forezi, L.S.M.; Cavalcante, V.G.S.; Juliani, C.S.R.; Resende, J.A.L.C.; da Rocha, D.R.; da Silva, F.C.; Ferreira, V.F. Synthesis of new xanthenes based on lawsone and coumarin via a tandem three-component reaction. J. Braz. Chem. Soc., 2017, 28, 1926-1936.
[http://dx.doi.org/10.21577/0103-5053.20170032]
[35]
Tisseh, Z.N.; Bazgir, A. An efficient, clean synthesis of 3,3′-(arylmethylene)bis(2-hydroxynaphthalene-1,4-dione) derivatives. Dyes Pigments, 2009, 83, 258-261.
[http://dx.doi.org/10.1016/j.dyepig.2008.09.003]
[36]
Sharma, G.; Vasanth Kumar, S.; Wahab, H.A. Molecular docking, synthesis, and biological evaluation of naphthoquinone as potential novel scaffold for H5N1 neuraminidase inhibition. J. Biomol. Struct. Dyn., 2018, 36(1), 233-242.
[http://dx.doi.org/10.1080/07391102.2016.1274271] [PMID: 28013578]
[37]
Brahmachari, G. Sulfamic acid-catalyzed one-pot room temperature synthesis of biologically relevant bis-lawsone derivatives. ACS Sustain. Chem. Eng., 2015, 39, 2058-2066.
[http://dx.doi.org/10.1021/acssuschemeng.5b00325]
[38]
Oku, H.; Kato, T.; Ishiguro, K. Antipruritic effects of 1,4-naphthoquinones and related compounds. Biol. Pharm. Bull., 2002, 25(1), 137-139.
[http://dx.doi.org/10.1248/bpb.25.137] [PMID: 11824545]
[39]
Costa, M.O.; Beltrame, C.O.; Ferreira, F.A.; Botelho, A.M.; Lima, N.C.; Souza, R.C.; de Almeida, L.G.; Vasconcelos, A.T.; Nicolás, M.F.; Figueiredo, A.M. Complete genome sequence of a variant of the methicillin-resistant Staphylococcus aureus ST239 lineage, strain BMB9393, displaying superior ability to accumulate ica-independent biofilm. Genome Announc., 2013, 1(4), 1-2.
[http://dx.doi.org/10.1128/genomeA.00576-13] [PMID: 23929475]
[40]
CLSI - Clinical and Laboratory Standard Institute. Performance standards for antimicrobial susceptibility testing in twenty-fifth informational supplement.. 2015, 35, 1.
[41]
Dobrovolskaia, M.A.; Germolec, D.R.; Weaver, J.L. Evaluation of nanoparticle immunotoxicity. Nat. Nanotechnol., 2009, 4(7), 411-414.
[http://dx.doi.org/10.1038/nnano.2009.175] [PMID: 19581891]
[42]
Yang, H.; Lou, C.; Sun, L.; Li, J.; Cai, Y.; Wang, Z.; Li, W.; Liu, G.; Tang, Y. admetSAR 2.0: web-service for prediction and optimization of chemical ADMET properties. Bioinformatics, 2019, 35(6), 1067-1069.
[http://dx.doi.org/10.1093/bioinformatics/bty707] [PMID: 30165565]
[43]
Forezi, L.S.M.; Marra, R.K.F.; da Silva, F.C.; Ferreira, V.F. Synthetic Strategies for Obtaining Xanthenes. Curr. Org. Synth., 2017, 14, 929-951.
[http://dx.doi.org/10.2174/1570179414666170825100808]
[44]
de Araújo, M.V.; de Souza, P.S.O.; de Queiroz, A.C.; da Matta, C.B.B.; Leite, A.B.; da Silva, A.E.; de França, J.A.A.; Silva, T.M.S.; Camara, C.A.; Alexandre-Moreira, M.S. Synthesis, leishmanicidal activity and theoretical evaluations of a series of substituted bis-2-hydroxy-1,4-naphthoquinones. Molecules, 2014, 19(9), 15180-15195.
[http://dx.doi.org/10.3390/molecules190915180] [PMID: 25247686]
[45]
Kossow, A.; Stühmer, B.; Schaumburg, F.; Becker, K.; Glatz, B.; Möllers, M.; Kampmeier, S.; Mellmann, A. High prevalence of MRSA and multi-resistant gram-negative bacteria in refugees admitted to the hospital-But no hint of transmission. PLoS One, 2018, 13(5)e0198103
[http://dx.doi.org/10.1371/journal.pone.0198103] [PMID: 29851962]
[46]
Nemeth, J.; Oesch, G.; Kuster, S.P. Bacteriostatic versus bactericidal antibiotics for patients with serious bacterial infections: systematic review and meta-analysis. J. Antimicrob. Chemother., 2015, 70(2), 382-395.
[http://dx.doi.org/10.1093/jac/dku379] [PMID: 25266070]
[47]
Thanigaimani, K.; Arshad, S.; Khalib, N.C.; Razak, I.A.; Arunagiri, C.; Subashini, A.; Sulaiman, S.F.; Hashim, N.S.; Ooi, K.L. A new chalcone structure of (E)-1-(4-Bromophenyl)-3-(napthalen-2-yl)prop-2-en-1-one: Synthesis, structural characterizations, quantum chemical investigations and biological evaluations. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2015, 149, 90-102.
[http://dx.doi.org/10.1016/j.saa.2015.04.028] [PMID: 25942090]
[48]
Evans, T.J. Small colony variants of Pseudomonas aeruginosa in chronic bacterial infection of the lung in cystic fibrosis. Future Microbiol., 2015, 10(2), 231-239.
[http://dx.doi.org/10.2217/fmb.14.107] [PMID: 25689535]
[49]
Ghai, I.; Ghai, S. Understanding antibiotic resistance via outer membrane permeability. Infect. Drug Resist., 2018, 11, 523-530.
[http://dx.doi.org/10.2147/IDR.S156995] [PMID: 29695921]
[50]
Rezende, C.O., Jr; Oliveira, L.A.; Oliveira, B.A.; Almeida, C.G.; Ferreira, B.S.; Le Hyaric, M.; Carvalho, G.S.; Lourenço, M.C.; Batista, M.; Marchini, F.K.; Silva, V.L.; Diniz, C.G.; Almeida, M.V. Synthesis and antibacterial activity of alkylated diamines and amphiphilic amides of quinic acid derivatives. Chem. Biol. Drug Des., 2015, 86(3), 344-350.
[http://dx.doi.org/10.1111/cbdd.12498] [PMID: 25528858]
[51]
Rojas, E.R.; Billings, G.; Odermatt, P.D.; Auer, G.K.; Zhu, L.; Miguel, A.; Chang, F.; Weibel, D.B.; Theriot, J.A.; Huang, K.C. The outer membrane is an essential load-bearing element in Gram-negative bacteria. Nature, 2018, 559(7715), 617-621.
[http://dx.doi.org/10.1038/s41586-018-0344-3] [PMID: 30022160]
[52]
Daneman, R.; Prat, A. The blood-brain barrier. Cold Spring Harb. Perspect. Biol., 2015, 7(1) a020412
[http://dx.doi.org/10.1101/cshperspect.a020412] [PMID: 25561720]
[53]
Nair, K.G.S.; Ramaiyan, V.; Sukumaran, S.K. Enhancement of drug permeability across blood brain barrier using nanoparticles in meningitis. Inflammopharmacology, 2018, 26(3), 675-684.
[http://dx.doi.org/10.1007/s10787-018-0468-y] [PMID: 29582240]
[54]
Pandit, N.; Singla, R.K.; Shrivastava, B. Current updates on oxazolidinone and its significance. Int. J. Med. Chem., 2012, 2012159285
[http://dx.doi.org/10.1155/2012/159285] [PMID: 25954524]
[55]
Choi, S.H.; Kim, E.Y.; Kim, Y.J. Systemic use of fluoroquinolone in children. Korean J. Pediatr., 2013, 56(5), 196-201.
[http://dx.doi.org/10.3345/kjp.2013.56.5.196] [PMID: 23741232]
[56]
Zhang, L.; Huang, Y.; Zhou, Y.; Buckley, T.; Wang, H.H. Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota. Antimicrob. Agents Chemother., 2013, 57(8), 3659-3666.
[http://dx.doi.org/10.1128/AAC.00670-13] [PMID: 23689712]
[57]
Raunio, H.; Kuusisto, M.; Juvonen, R.O.; Pentikäinen, O.T. Modeling of interactions between xenobiotics and cytochrome P450 (CYP) enzymes. Front. Pharmacol., 2015, 6, 123.
[http://dx.doi.org/10.3389/fphar.2015.00123] [PMID: 26124721]


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VOLUME: 20
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Year: 2020
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DOI: 10.2174/1568026619666191210160342
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