Synthesis and In vitro Antibacterial, Antitubercular Studies of Novel Fluoroquinolones Analogs Containing 4-substituted Sec Amine

Author(s): Ravi K. Akula*, Shanthan R. Pamulaparthy, Pranay K. Koochana, Dharmarajan Sriram

Journal Name: Current Bioactive Compounds

Volume 15 , Issue 6 , 2019

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Graphical Abstract:


Abstract:

Background: Tuberculosis is a contagious, air borne disease and second leading cause of death among infectious diseases worldwide. Fluoroquinolones are well-known antibacterial agents and they were recommended as second-line of antitubercular drugs.

Method: A series of novel fluoroquinolone analogs 6-24 was effectively synthesized. An attempt was made by tagging the substituted pyrazole on to fluoroquinolones for the first time at C-7 position. The newly synthesized compounds were characterized by FTIR, 1HNMR, ESI-MS, HR-MS and elemental analysis. The in vitro antibacterial activity of all the title compounds was investigated against various gram positive, gram negative bacterial organisms and in vitro antitubercular activity against Mycobacterium Tuberculosis H37Rv strain.

Result: Most of the synthesized compounds showed comparable activity against the entire gram positive and gram negative bacterial organisms. Fluoroquinolone 16 showed enhanced activity against both type of bacterial strains and compound 11showed promising activity against MTB-H37Rv strain.

Conclusion: Some of the novel fluoroquinolone analogs (11, 16) showed potent antibacterial, antitubercular activity.

Keywords: Fluoroquinolones, Tuberculosis, Antimicrobial activity, 2-(Piperidin-4-yl)-1H-benzo[d] imidazole, pharmacokinetic, benzimidazole.

[1]
WHO Global Tuberculosis Report. www.who.int/tb/publications/factsheet_global.pdf [Accessed Mar 2017].
[2]
Tomioka, H. Current status of some antituberculosis drugs and the development of new antituberculous agents with special reference to their in vitro and in vivo antimicrobial activities. Curr. Pharm. Des., 2006, 12(31), 4047-4070.
[http://dx.doi.org/10.2174/138161206778743646] [PMID: 17100611]
[3]
Maher, D.; Raviglione, M. Global epidemiology of tuberculosis. Clin. Chest Med., 2005, 26(2), 167-182. v.
[http://dx.doi.org/10.1016/j.ccm.2005.02.009] [PMID: 15837103]
[4]
Frieden, T.R.; Munsiff, S.S. The dots strategy for controlling the global tuberculosis epidemic. Clin. Chest Med., 2005, 26(2), 197-205. v.
[http://dx.doi.org/10.1016/j.ccm.2005.02.001] [PMID: 15837105]
[5]
Braunstein, M.; Bardarov, S.S.; Jacobs, W.R. Jr Genetic methods for deciphering virulence determinants of Mycobacterium tuberculosis. Methods Enzymol., 2002, 358, 67-99.
[http://dx.doi.org/10.1016/S0076-6879(02)58081-2] [PMID: 12474379]
[6]
Chu, D.T.; Fernandes, P.B. Structure-activity relationships of the fluoroquinolones. Antimicrob. Agents Chemother., 1989, 33(2), 131-135.
[http://dx.doi.org/10.1128/AAC.33.2.131] [PMID: 2655528]
[7]
Hong, C.Y.; Kim, Y.K.; Chang, J.H.; Kim, S.H.; Choi, H.; Nam, D.H.; Kim, Y.Z.; Kwak, J.H. Novel fluoroquinolone antibacterial agents containing oxime-substituted (aminomethyl)pyrrolidines: Synthesis and antibacterial activity of 7-(4-(aminomethyl)-3-(methoxyimino)pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid (LB20304). J. Med. Chem., 1997, 40(22), 3584-3593.
[http://dx.doi.org/10.1021/jm970202e] [PMID: 9357525]
[8]
North, D.S.; Fish, D.N.; Redington, J.J. Levofloxacin, a second-generation fluoroquinolone. Pharmacotherapy, 1998, 18(5), 915-935.
[PMID: 9758306]
[9]
Anquetin, G.; Greiner, J.; Mahmoudi, N.; Santillana-Hayat, M.; Gozalbes, R.; Farhati, K.; Derouin, F.; Aubry, A.; Cambau, E.; Vierling, P. Design, synthesis and activity against Toxoplasma gondii, Plasmodium spp., and Mycobacterium tuberculosis of new 6-fluoroquinolones. Eur. J. Med. Chem., 2006, 41(12), 1478-1493.
[http://dx.doi.org/10.1016/j.ejmech.2006.07.003] [PMID: 17000032]
[10]
Guidelines, W.H.O. Guidelines for the management of drug-resistant tuberculosis, WHO/TB/96-210 (rev.1); World Health Organization: Geneva, 1997.
[11]
Zhao, Y.L.; Chen, Y.L.; Sheu, J.Y.; Chen, I.L.; Wang, T.C.; Tzeng, C.C. Synthesis and antimycobacterial evaluation of certain fluoroquinolone derivatives. Bioorg. Med. Chem., 2005, 13(12), 3921-3926.
[http://dx.doi.org/10.1016/j.bmc.2005.04.005] [PMID: 15911308]
[12]
Maurício, F.S.; Marcus, V.N. de Souza.; Marie, E.T.H.D.; Débora P.A.; Gustavo, S.G. de C.; Mauro V. de A. Synthesis and antitubercular evaluation of new fluoroquinolone derivatives coupled with carbohydrates. Carbohydr. Res., 2010, 345, 761-767.
[http://dx.doi.org/10.1016/j.carres.2010.01.016]
[13]
Kapil, M.A.; Gokul, S.T. Synthesis and antibacterial, antimycobacterial and docking studies of novel N-piperazinyl fluoroquinolones. Med. Chem. Res., 2013, 22, 818-832.
[http://dx.doi.org/10.1007/s00044-012-0074-2]
[14]
Mohammad, A.; Anees, A.S.; Asif, H. Quinolone derivatives as antitubercular drugs. Med. Chem. Res., 2013, 22, 1029-1042.
[http://dx.doi.org/10.1007/s00044-012-0101-3]
[15]
Zhang, L.; Addla, D.; Ponmani, J.; Wang, A.; Xie, D.; Wang, Y.N.; Zhang, S.L.; Geng, R.X.; Cai, G.X.; Li, S.; Zhou, C.H. Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents. Eur. J. Med. Chem., 2016, 111, 160-182.
[http://dx.doi.org/10.1016/j.ejmech.2016.01.052] [PMID: 26871658]
[16]
Kumar, A.R.; Sathaiah, G.; Shekhar, A.C.; Raju, K.; Rao, P.S.; Narsaiah, B.; Raju, Y.K.; Murthy, U.S.N.; Srimai, V.; Ramesh, M.; Parthasarathy, T. Synthesis of 6-fluoro-7-cyclic amino substituted dicarboxylic acid quinolones and their antibacterial activity. J. Heterocycl. Chem., 2014, 51, E114-E122.
[http://dx.doi.org/10.1002/jhet.1889]
[17]
Kumar, A.R.; Sathaiah, G.; Shekhar, A.C.; Raju, K.; Rao, P.S.; Narsaiah, B.; Raju, Y.K.; Murthy, U.S.N. Synthesis of novel nalkyl triazole substituted fluoroquinolones and their antimicrobial activity. J. Heterocycl. Chem., 2015, 52, 235-242.
[http://dx.doi.org/10.1002/jhet.2034]
[18]
Beulah, K.; Kumar, A.R.; Lingaiah, B.P.V.; Rao, P.S.; Narsaiah, B.; Reddy, A.S.K.; Murty, U.S.N. Design, synthesis and biological evaluation of benzimidazole-pyridine-piperidine hybrids as a new class of potent antimicrobial agents. Lett. Drug Des. Discov., 2015, 12, 38-42.
[http://dx.doi.org/10.2174/1570180811666140725185713]
[19]
Reddy, G.V.; Kanth, S.R.; Maitraie, D.; Narsaiah, B.; Rao, P.S.; Kishore, K.H.; Murthy, U.S.N.; Ravi, B.; Kumar, B.A.; Parthasarathy, T. Design, synthesis, structure-activity relationship and antibacterial activity series of novel imidazo fused quinolone carboxamides. Eur. J. Med. Chem., 2009, 44(4), 1570-1578.
[http://dx.doi.org/10.1016/j.ejmech.2008.07.024] [PMID: 18775585]
[20]
Kumar, A.R.; Lingaiah, B.P.V.; Rao, P.S.; Narsaiah, B.; Sriram, D.; Sowjanya, P. Synthesis and biological evaluation of novel N1-decyl and C7- Sec amine substituted fluoroquinolones as antitubercular and anticancer agents. Indian J. Chem., 2015, 54B, 1495-1501.
[21]
Koga, H.; Itoh, A.; Murayama, S.; Suzue, S.; Irikura, T. Structure-activity relationships of antibacterial 6,7- and 7,8-disubstituted 1-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids. J. Med. Chem., 1980, 23(12), 1358-1363.
[http://dx.doi.org/10.1021/jm00186a014] [PMID: 7452690]
[22]
Niedermeier, S.; Singethan, K.; Rohrer, S.G.; Matz, M.; Kossner, M.; Diederich, S.; Maisner, A.; Schmitz, J.; Hiltensperger, G.; Baumann, K.; Holzgrabe, U.; Schneider-Schaulies, J. A small-molecule inhibitor of Nipah virus envelope protein-mediated membrane fusion. J. Med. Chem., 2009, 52(14), 4257-4265.
[http://dx.doi.org/10.1021/jm900411s] [PMID: 19499921]
[23]
Almasirad, A.; Tabatabai, S.A.; Faizi, M.; Kebriaeezadeh, A.; Mehrabi, N.; Dalvandi, A.; Shafiee, A. Synthesis and anticonvulsant activity of new 2-substituted-5- [2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles. Bioorg. Med. Chem. Lett., 2004, 14(24), 6057-6059.
[http://dx.doi.org/10.1016/j.bmcl.2004.09.072] [PMID: 15546729]
[24]
Pokrovskaya, V.; Belakhov, V.; Hainrichson, M.; Yaron, S.; Baasov, T. Design, synthesis, and evaluation of novel fluoroquinolone-aminoglycoside hybrid antibiotics. J. Med. Chem., 2009, 52(8), 2243-2254.
[http://dx.doi.org/10.1021/jm900028n] [PMID: 19301822]
[25]
Guo, Q.; Liu, M.L.; Feng, L.S.; Lv, K.; Guan, Y.; Guo, H.Y.; Xiao, C.L. Synthesis and in-vitro antimycobacterial activity of fluoroquinolone derivatives containing a coumarin moiety. Arch. Pharm., (Weinheim), 2011, 344, 802-809.
[26]
Feng, L.S.; Liu, M.L.; Zhang, S.; Chai, Y.; Wang, B.; Zhang, Y.B.; Lv, K.; Guan, Y.; Guo, H.Y.D.; Xiao, C.L. Synthesis and in vitro antimycobacterial activity of 8-OCH(3) ciprofloxacin methylene and ethylene isatin derivatives. Eur. J. Med. Chem., 2011, 46(1), 341-348.
[http://dx.doi.org/10.1016/j.ejmech.2010.11.023] [PMID: 21146257]
[27]
Rathelot, P.; Azas, N.; El-Kashef, H.; Delmas, F.; Di Giorgio, C.; Timon-David, P.; Maldonado, J.; Vanelle, P. 1,3-Diphenylpyrazoles: Synthesis and antiparasitic activities of azomethine derivatives. Eur. J. Med. Chem., 2002, 37(8), 671-679.
[http://dx.doi.org/10.1016/S0223-5234(02)01388-0] [PMID: 12161064]
[28]
Bekhit, A.A.; Fahmy, H.T.; Rostom, S.A.; El-Din, A.; Bekhit, A.; Bekhit, A. Synthesis and biological evaluation of some thiazolylpyrazole derivatives as dual anti-inflammatory antimicrobial agents. Eur. J. Med. Chem., 2010, 45(12), 6027-6038.
[http://dx.doi.org/10.1016/j.ejmech.2010.10.001] [PMID: 20970223]
[29]
Zheng, C.J.; Xu, L.L.; Sun, L.P.; Miao, J.; Piao, H.R. Synthesis and antibacterial activity of novel 1,3-diphenyl-1H-pyrazoles functionalized with phenylalanine-derived rhodanines. Eur. J. Med. Chem., 2012, 58, 112-116.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.012] [PMID: 23123727]
[30]
Kira, M.A.; Abdel-Rahman, M.O.; Gadalla, K.Z. The vilsmeier-haack reaction - III cyclization of hydrazones to pyrazoles. Tet. Lett., 1969, 10, 109-110.
[http://dx.doi.org/10.1016/S0040-4039(01)88217-4]
[31]
Ferraro, M.J. Methods for Dilution Antimicrobial susceptibility tests for bacteria, which grows aerobically, 5thEd.; National Committee for Clinical Laboratory Standards: Pennsylvania . , 2000.
[32]
White, D.G.; Hudson, C.; Maurer, J.J.; Ayers, S.; Zhao, S.; Lee, M.D.; Bolton, L.; Foley, T.; Sherwood, J. Characterization of chloramphenicol and florfenicol resistance in Escherichia coli associated with bovine diarrhea. J. Clin. Microbiol., 2000, 38(12), 4593-4598.
[PMID: 11101601]
[33]
Wayne, P.A. Antimycobacterial susceptibility testing for Mycobacterium tuberculosis; Tentative standard M24-T. National Committee for Clinical Laboratory Standards: Pennsylvania,; , 1995.
[34]
Alokam, R.; Jeankumar, V.U.; Sridevi, J.P.; Matikonda, S.S.; Peddi, S.; Alvala, M.; Yogeeswari, P.; Sriram, D. Identification and structure-activity relationship study of carvacrol derivatives as Mycobacterium tuberculosis chorismate mutase inhibitors. J. Enzyme Inhib. Med. Chem., 2014, 29(4), 547-554.
[http://dx.doi.org/10.3109/14756366.2013.823958] [PMID: 24090423]


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VOLUME: 15
ISSUE: 6
Year: 2019
Page: [656 - 664]
Pages: 9
DOI: 10.2174/1573407214666180529124816
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