Towards eradicating antibiotic-resistant bacteria: synthesis and antibacterial activities of substituted N-(2-nitrophenyl)pyrrolidine- and piperidine-2-carboxylic acids

doi:10.5246/jcps.2019.10.067

中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (10): 704-715.DOI: 10.5246/jcps.2019.10.067

Towards eradicating antibiotic-resistant bacteria: synthesis and antibacterial activities of substituted N-(2-nitrophenyl)pyrrolidine- and piperidine-2-carboxylic acids

Jocelyn A. Odusami^1,2,3, Monisola I. Ikhile^2*, Marthe C. D. Fotsing², Idris A. Olasupo³, Josephat U. Izunobi³, Elizabeth O. Bamgbade^2,3, Thierry Y. Fonkui⁴, Olayinka T. Asekun³, Oluwole B. Familoni^3*, Derek T. Ndinteh^2*

1. Department of Chemical Sciences, Yaba College of Technology, Yaba, Lagos, Nigeria
2. Department of Applied Chemistry, P.O Box 17011, Doornfontein Campus 2028, University of Johannesburg, South Africa
3. Department of Chemistry, University of Lagos, Akoka, Lagos, Nigeria
4. Department of Biotechnology and Food Technology, P.O Box 17011, Doornfontein Campus 2028, University of Johannesburg, South Africa

收稿日期:2019-06-20 修回日期:2019-08-23 出版日期:2019-10-31 发布日期:2019-09-15
通讯作者: E-mail: miikhile@gmail.com; familonio@unilag.edu.ng; dndinteh@uj.ac.za
基金资助:
Department of Applied Chemistry, Faculty of Science, University of Johannesburg for providing chemicals and running cost for this project through the National Research Foundation (NRF).

Towards eradicating antibiotic-resistant bacteria: synthesis and antibacterial activities of substituted N-(2-nitrophenyl)pyrrolidine- and piperidine-2-carboxylic acids

1. Department of Chemical Sciences, Yaba College of Technology, Yaba, Lagos, Nigeria
2. Department of Applied Chemistry, P.O Box 17011, Doornfontein Campus 2028, University of Johannesburg, South Africa
3. Department of Chemistry, University of Lagos, Akoka, Lagos, Nigeria
4. Department of Biotechnology and Food Technology, P.O Box 17011, Doornfontein Campus 2028, University of Johannesburg, South Africa

Received:2019-06-20 Revised:2019-08-23 Online:2019-10-31 Published:2019-09-15
Contact: E-mail: miikhile@gmail.com; familonio@unilag.edu.ng; dndinteh@uj.ac.za
Supported by:
Department of Applied Chemistry, Faculty of Science, University of Johannesburg for providing chemicals and running cost for this project through the National Research Foundation (NRF).

摘要/Abstract

摘要：

Antibacterial resistance is a source of great concern in the effective prevention and treatment of infections caused by bacteria, making the development of requisite therapeutics a major challenge. N-(Nitrophenyl)cycloamino acids are important compounds in the synthesis of poly-condensed nitrogen-containing heterocycles with marked activities in many biological systems. A series of substituted N-(o-nitrophenyl)cycloamino-2-carboxylic acids 3a–3g were synthesized via the condensation reaction of substituted o-halogenonitrobenzenes with L-proline 2a and D,L-pipecolinic acid 2b, under refluxing alcoholic basic conditions in excellent yields. The synthesized compounds were characterised by FT-IR, (¹H & ¹³C) NMR, UV-Vis, mass spectroscopy and elemental analysis. Their antibacterial activities were evaluated against five Gram-positive and five Gram-negative bacterial strains using the broth micro-dilution procedure. The antibacterial activities of the synthesized compounds were compared with streptomycin and nalidixic acid as standard antibiotic drugs. The minimum inhibitory concentration (MIC) values of compounds 3a–3g revealed good antibacterial activities against the tested microorganisms. Compounds 3a–3g were more potent than nalidixic acid against Enterococcus faecalis, Mycobacterium smegmatis, Escherichia coli and Proteus vulgaris and also more potent than streptomycin against Enterobacter cloacae and Staphylococcus aureus. Compounds 3a, 3c and 3g displayed the highest antibacterial potency with an MIC value of 15.6 μg/mL against E. cloacae, E. faecalis and P. mirabilis, respectively. These results indicated that these aryl cycloamino acids with antibacterial activities had potential applications as substitutes for antimicrobial peptide antibiotics, which are not susceptible to bacterial resistance, to solve the problem of drug resistance.

关键词: Antibiotics, Bacteria, Cyclic amino acids, o-Halogenonitrobenzene

Abstract:

Key words: Antibiotics, Bacteria, Cyclic amino acids, o-Halogenonitrobenzene

中图分类号:

R914

Supporting:

Jocelyn A. Odusami, Monisola I. Ikhile, Marthe C. D. Fotsing, Idris A. Olasupo, Josephat U. Izunobi, Elizabeth O. Bamgbade, Thierry Y. Fonkui. Towards eradicating antibiotic-resistant bacteria: synthesis and antibacterial activities of substituted N-(2-nitrophenyl)pyrrolidine- and piperidine-2-carboxylic acids[J]. 中国药学(英文版), 2019, 28(10): 704-715.

参考文献

[1] World Health Organisation (WHO), Fact sheet on antibiotic resistance, 2018, https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance

[2] Vargas-Casanova, Y.; Rodríguez-Mayor, A.V.; Cardenas, K.J.; Leal-Castro, A.L.; Muñoz-Molina, L.C.; Fierro-Medina, R.; Rivera-Monroy, Z.J.; García-Castañeda, J.E. Synergistic bactericide and antibiotic effects of dimeric, tetrameric, or palindromic peptides containing the RWQWR motif against Gram-positive and Gram-negative strains. RSC Adv. 2019, 9, 7239-7245.

[3] Zhou, C.C.; Zhou, X.Y.; Su, X.K. Noncytotoxic poly-caprolactone-polyethyleneglycol-ε-poly(l-lysine) triblock copolymer synthesized and self-assembled as an antibacterial drug carrier. RSC Adv. 2017, 7, 39718-39725.

[4] Ganley, J.G.; Carr, G.; Ioerger, T.R.; Sacchettini, J.C.; Clardy, J.; Derbyshire, E.R. Discovery of antimicrobial lipodepsipeptides produced by a serratia sp. within mosquito microbiomes. ChemBioChem. 2018, 19, 1590-1594.

[5] Zhang, L.J.; Gallo, R.L. Antimicrobial peptides. Curr. Biol. 2016, 26, R14-R19.

[6] Abu-Hashem, A.A.; Gouda, M.A.; Badria, F.A. Synthesis of some new pyrimido[2', 1': 2, 3]thiazolo[4, 5-B]quinoxaline derivatives as anti-inflammatory and analgesic agents. Eur. J. Med. Chem. 2010, 45, 1976-1981.

[7] El-Tombary, A.A.; El-Hawash, S.A. Synthesis, antioxidant, anticancer and antiviral activities of novel quinoxaline hydrazone derivatives and their acyclic C-nucleosides. Med. Chem. 2014, 10, 521-532.

[8] Jonet, A.; Guillon, J.; Mullie, C.; Cohen, A.; Bentzinger, G.; Schneider, J.; Taudon, N.; Hutter, S.; Azas, N.; Moreau, S.; Savrimoutou, S.; Agnamey, P.; Dassonville-Klimpt, A.; Sonnet, P. Synthesis and Antimalarial Activity of New Enantiopure Aminoalcoholpyrrolo[1, 2-a]quinoxalines. Med. Chem. 2018, 14, 293-303.

[9] Prasad, B.; Shiva Kumar, K.; Vijaya Babu, P.; Anusha, K.; Rambabu, D.; Kandale, A.; Vanaja, G.R.; Kalle, A.M.; Pal, M. AlCl3 induced C-N bond formation followed by Pd/C-Cu mediated coupling-cyclization strategy: synthesis of pyrrolo[2, 3-b]quinoxalines as anticancer agents. Tetrahedron Lett. 2012, 53, 6059-6066.

[10] Farrag, A.A.S.; Ammar, Y.A.; El-Sehemi, A.A.G.; Thabet, H.K.; Hassan, N.A.A.; Samy, A.K. Synthesis, and pharmacological screening of novel sulfamoylphenylcar-bamoylquinoxaline derivatives as anti-inflammatory, analgesic and antitumour agents. J. Chem. Res. 2011, 35, 163-166.

[11] Kumar, K.S.; Rambabu, D.; Sandra, S.; Kapavarapu, R.; Krishna, G.R.; Basaveswara Rao, M.V.; Chatti, K.; Reddy, C.M.; Misra, P.; Pal, M. AlCl3 induced (hetero)arylation of 2, 3-dichloroquinoxaline: a one-pot synthesis of mono/disubstituted quinoxalines as potential antitubercular agents. Bioorg. Med. Chem. 2012, 20, 1711-1722.

[12] Ramalingam, P.; Ganapaty, S.; Rao, C.h.B. In vitro antitubercular and antimicrobial activities of 1-substituted quinoxaline-2, 3(1H, 4H)-diones. Bioorg. Med. Chem. Lett. 2010, 20, 406-408.

[13] Al-Marhabi, A.R.; Abbas, H.A.; Ammar, Y.A. Synthesis, characterization and biological evaluation of some quinoxaline derivatives: A promising and potent new class of antitumor and antimicrobial agents. Molecules 2015, 20, 19805-19822.

[14] Clinical Laboratory Standards Institute (CLSI). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard-Second Edition: CLSI Document M38-A2. CLSI, Wayne, PA, USA, 2008, 35.

[15] Olatunde S,O. Synthesis of 4-aminoantipyrine Schiff bases and their antimicrobial activities. J. Chin. Pharm. Sci. 2018, 27, 753-766.

[16] Alo, B. I.; Ewedemi, R.; Familoni, O. B. Polycyclic nitrogen compounds. Part 6, Synthesis of new benzo-substituted angular tricyclic quinoxalinones. Bull. Chem. Soc. Nig. 1987, 12, 1-10.

[17] Schlosser, M.; Ruzziconi, R. Nucleophilic substitutions of nitroarenes and pyridines: new insight and new applications. Synthesis. 2010, 2010, 2111-2123.

[18] Sowole, M.A.; Adebisi, A.B.; Olasupo, I.A.; Izunobi, J.U.; Familoni, O.B. Microwave-Assisted Solvent-Free Arylation of Amino acids with Halogenobenzenes. J. Chem. Soc. Nigeria. 2018, 43, 345-352.

[19] Mei, L.; Hu, J.; Cao, X.D.; Wang, F.F.; Zheng, C.; Tao, Y.T.; Zhang, X.W.; Huang, W. The inductive-effect of electron withdrawing trifluoromethyl for thermally activated delayed fluorescence: tunable emission from tetra- to penta-carbazole in solution processed blue OLEDs. Chem. Commun. (Camb). 2015, 51, 13024-13027.

[20] Kayaoglu, G.; Ørstavik, D. Virulence factors of Enterococcus faecalis: relationship to endodontic disease. Crit. Rev. Oral Biol. Med. 2004, 15, 308-320.

[21] Akanbi, O.E.; Njom, H.A.; Fri, J.; Otigbu, A.C.; Clarke, A.M. Antimicrobial susceptibility of staphylococcus aureus isolated from recreational Waters and beach sand in Eastern cape province of South Africa. Int. J. Environ. Res. Public. Health. 2017, 14, E1001.

[22] Nataro, J.P.; Steiner, T.; Guerrant, R.L. Enteroaggregative escherichia coli. Emerg. Infect. Dis. 1998, 4, 251-261.

[23] Andrews, J.M. Determination of minimum inhibitory concentrations. J. Antimicrob. Chemother. 2001, 48, 5-16.

[24] Fonkui, T.Y; Ikhile, M.I.; Muganza, F.M.; Fotsing, M.C.D.; Siwe-Noundou, X.; Krause, R.W.M.; Arderne, C.; Ndinteh, D.T.; Njobeh, P.B. Synthesis, characterization and biological applications of novel Schiff bases of 2-(Trifluoromethoxy) aniline. J. Chin. Pharm. Sci. 2018, 27, 307-323.

Towards eradicating antibiotic-resistant bacteria: synthesis and antibacterial activities of substituted N-(2-nitrophenyl)pyrrolidine- and piperidine-2-carboxylic acids

Towards eradicating antibiotic-resistant bacteria: synthesis and antibacterial activities of substituted N-(2-nitrophenyl)pyrrolidine- and piperidine-2-carboxylic acids

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