Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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

4H-1,3-Benzothiazin-4-one a Promising Class Against MDR/XDR-TB

Author(s): Marcus Vinicius Nora de Souza* and Thais Cristina Mendonça Nogueira

Volume 19, Issue 8, 2019

Page: [567 - 578] Pages: 12

DOI: 10.2174/1568026619666190305130809

Price: $65

Abstract

Nowadays, tuberculosis (TB) is an important global public health problem, being responsible for millions of TB-related deaths worldwide. Due to the increased number of cases and resistance of Mycobacterium tuberculosis to all drugs used for the treatment of this disease, we desperately need new drugs and strategies that could reduce treatment time with fewer side effects, reduced cost and highly active drugs against resistant strains and latent disease. Considering that, 4H-1,3-benzothiazin-4-one is a promising class of antimycobacterial agents in special against TB-resistant strains being the aim of this review the discussion of different aspects of this chemical class such as synthesis, mechanism of action, medicinal chemistry and combination with other drugs.

Keywords: Tuberculosis, Drugs, 4H-1, 3-benzothiazin-4-one, Synthesis, Mycobacterium tuberculosis, Multi drug resistant.

« Previous Next »
Graphical Abstract

[1]
Zhang, Y.; Yew, W.W. Mechanisms of drug resistance in Mycobacterium tuberculosis. Int. J. Tuberc. Lung Dis., 2009, 13(11), 1320-1330. [PMID: 19861002].
[2]
WHO. Multidrug and extensively drug-resistant TB (M/XDR-TB): 2010 Global Report on Surveillance and response; World Health Organization: Geneva, Switzerland, 2010.
[3]
WHO TB drug resistance types.(Accessed at, http://www.who.int/ tb/areas-of-work/drug-resistant-tb/types/en/
[4]
WHO. Totally Drug-Resistant TB.A WHO consultation on the diagnostic definition and treatment options; World Health Organization: Geneva, Switzerland, 2012.
[5]
Ginsberg, A.M. Drugs in development for tuberculosis. Drugs, 2010, 70(17), 2201-2214. [http://dx.doi.org/10.2165/11538170-000000000-00000]. [PMID: 21080738].
[6]
Villemagne, B.; Crauste, C.; Flipo, M.; Baulard, A.R.; Déprez, B.; Willand, N. Tuberculosis: The drug development pipeline at a glance. Eur. J. Med. Chem., 2012, 51(0), 1-16. [http://dx.doi.org/ 10.1016/j.ejmech.2012.02.033]. [PMID: 22421275].
[7]
European Medicines Agency. 2010. (Accessed at. http://www. ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2010/06/WC500094022.pdf
[8]
FDA Application No. 204384. 2012. (Accessed at https://www. accessdata.fda.gov/drugsatfda_docs/nda/2012/204384Orig1s000 SumR.pdf
[9]
Andries, K.; Verhasselt, P.; Guillemont, J.; Göhlmann, H.W.; Neefs, J.M.; Winkler, H.; Van Gestel, J.; Timmerman, P.; Zhu, M.; Lee, E.; Williams, P.; de Chaffoy, D.; Huitric, E.; Hoffner, S.; Cambau, E.; Truffot-Pernot, C.; Lounis, N.; Jarlier, V. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science, 2005, 307(5707), 223-227. [http://dx.doi.org/ 10.1126/science.1106753]. [PMID: 15591164].
[10]
Pasca, M.R.; Degiacomi, G.; Ribeiro, A.L.D.J.L.; Zara, F.; De Mori, P.; Heym, B.; Mirrione, M.; Brerra, R.; Pagani, L.; Pucillo, L.; Troupioti, P.; Makarov, V.; Cole, S.T.; Riccardi, G. Clinical isolates of Mycobacterium tuberculosis in four European hospitals are uniformly susceptible to benzothiazinones. Antimicrob. Agents Chemother., 2010, 54(4), 1616-1618. [http://dx.doi.org/10.1128/ AAC.01676-09]. [PMID: 20086151].
[11]
Makarov, V.; Cole, S.T.; Moellmann, U. New Benzothiazinone derivatives and their use as antibacterial agents. Germany, WO2007134625A1,, 2007.
[12]
New, T.B. Drugs, Clinical Pipeline. 2018. (Accessed at https://www.newtbdrugs.org/pipeline/clinical
[13]
Makarov, V.; Manina, G.; Mikusova, K.; Möllmann, U.; Ryabova, O.; Saint-Joanis, B.; Dhar, N.; Pasca, M.R.; Buroni, S.; Lucarelli, A.P.; Milano, A.; De Rossi, E.; Belanova, M.; Bobovska, A.; Dianiskova, P.; Kordulakova, J.; Sala, C.; Fullam, E.; Schneider, P.; McKinney, J.D.; Brodin, P.; Christophe, T.; Waddell, S.; Butcher, P.; Albrethsen, J.; Rosenkrands, I.; Brosch, R.; Nandi, V.; Bharath, S.; Gaonkar, S.; Shandil, R.K.; Balasubramanian, V.; Balganesh, T.; Tyagi, S.; Grosset, J.; Riccardi, G.; Cole, S.T. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science, 2009, 324(5928), 801-804. [http://dx.doi.org/10.1126/science.1171583]. [PMID: 19299584].
[14]
Trefzer, C.; Rengifo-Gonzalez, M.; Hinner, M.J.; Schneider, P.; Makarov, V.; Cole, S.T.; Johnsson, K. Benzothiazinones: Prodrugs that covalently modify the decaprenylphosphoryl-β-D-ribose 2′-epimerase DprE1 of Mycobacterium tuberculosis. J. Am. Chem. Soc., 2010, 132(39), 13663-13665. [http://dx.doi.org/10.1021/ ja106357w]. [PMID: 20828197].
[15]
Manina, G.; Pasca, M.R.; Buroni, S.; De Rossi, E.; Riccardi, G. Decaprenylphosphoryl-β-D-ribose 2′-epimerase from Mycobacterium tuberculosis is a magic drug target. Curr. Med. Chem., 2010, 17(27), 3099-3108. [http://dx.doi.org/10.2174/09298671079 1959693]. [PMID: 20629622].
[16]
Neres, J.; Pojer, F.; Molteni, E.; Chiarelli, L.R.; Dhar, N.; Boy-Röttger, S.; Buroni, S.; Fullam, E.; Degiacomi, G.; Lucarelli, A.P.; Read, R.J.; Zanoni, G.; Edmondson, D.E.; De Rossi, E.; Pasca, M.R.; McKinney, J.D.; Dyson, P.J.; Riccardi, G.; Mattevi, A.; Cole, S.T.; Binda, C. Structural basis for benzothiazinone-mediated killing of Mycobacterium tuberculosis. Sci. Transl. Med., 2012, 4(150)150ra121 [http://dx.doi.org/10.1126/scitranslmed.3004395]. [PMID: 22956199].
[17]
Foo, C.S.; Lechartier, B.; Kolly, G.S.; Boy-Röttger, S.; Neres, J.; Rybniker, J.; Lupien, A.; Sala, C.; Piton, J.; Cole, S.T. Characterization of DprE1-mediated benzothiazinone resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 2016, 60(11), 6451-6459. [http://dx.doi.org/10.1128/AAC.01523-16]. [PMID: 27527085].
[18]
Trefzer, C.; Rengifo-Gonzalez, M.; Hinner, M.J.; Schneider, P.; Makarov, V.; Cole, S.T.; Johnsson, K. Benzothiazinones: Prodrugs that covalently modify the decaprenylphosphoryl-β-D-ribose 2′-epimerase DprE1 of Mycobacterium tuberculosis. J. Am. Chem. Soc., 2010, 132(39), 13663-13665. [http://dx.doi.org/10.1021/ ja106357w]. [PMID: 20828197].
[19]
Trefzer, C.; Škovierová, H.; Buroni, S.; Bobovská, A.; Nenci, S.; Molteni, E.; Pojer, F.; Pasca, M.R.; Makarov, V.; Cole, S.T.; Riccardi, G.; Mikušová, K.; Johnsson, K. Benzothiazinones are suicide inhibitors of mycobacterial decaprenylphosphoryl-β-D-ribofu-ranose 2′-oxidase DprE1. J. Am. Chem. Soc., 2012, 134(2), 912-915. [http://dx.doi.org/10.1021/ja211042r]. [PMID: 22188377].
[20]
Batt, S.M.; Jabeen, T.; Bhowruth, V.; Quill, L.; Lund, P.A.; Eggeling, L.; Alderwick, L.J.; Fütterer, K.; Besra, G.S. Structural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors. Proc. Natl. Acad. Sci. USA, 2012, 109(28), 11354-11359. [http://dx.doi.org/10.1073/pnas.1205735109]. [PMID: 22733761].
[21]
Batt, S.M.; Jabeen, T.; Bhowruth, V.; Quill, L.; Lund, P.A.; Eggeling, L.; Alderwick, L.J.; Fütterer, K.; Besra, G.S. Structural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors. Proc. Natl. Acad. Sci. USA, 2012, 109(28), 11354-11359. [http://dx.doi.org/10.1073/pnas.1205735109]. [PMID: 22733761].
[22]
Grover, S.; Alderwick, L.J.; Mishra, A.K.; Krumbach, K.; Marienhagen, J.; Eggeling, L.; Bhatt, A.; Besra, G.S. Benzothiazinones mediate killing of Corynebacterineae by blocking decaprenyl phosphate recycling involved in cell wall biosynthesis. J. Biol. Chem., 2014, 289(9), 6177-6187. [http://dx.doi.org/10.1074/ jbc.M113. 522623]. [PMID: 24446451].
[23]
Piton, J.; Foo, C.S.; Cole, S.T. Structural studies of Mycobacterium tuberculosis DprE1 interacting with its inhibitors. Drug Discov. Today, 2017, 22(3), 526-533. [http://dx.doi.org/10.1016/ j.drudis.2016.09.014]. [PMID: 27666194].
[24]
Kloss, F.; Krchnak, V.; Krchnakova, A.; Schieferdecker, S.; Dreisbach, J.; Krone, V.; Möllmann, U.; Hoelscher, M.; Miller, M.J. In Vivo dearomatization of the potent antituberculosis agent BTZ043 via meisenheimer complex formation. Angew. Chem. Int. Ed. Engl., 2017, 56(8), 2187-2191. [http://dx.doi.org/10.1002/ anie.201609-737]. [PMID: 28097740].
[25]
Rudolph, A.I. Antitubercular Benzothiazinones: Synthesis, activity, properties and SAR; Martin-Luther University, Halle-Wittenberg, 2014.
[26]
Shanshan, L.; Hailong, H.; Ning, Z.; Limin, H.; Jiayuan, L. Review about the synthesis of 1,3-benzothiazinone derivatives. Youji Huaxue, 2016, 36(9), 2024-2038. [http://dx.doi.org/10.6023/ cjoc201603034].
[27]
Karoli, T.; Becker, B.; Zuegg, J.; Möllmann, U.; Ramu, S.; Huang, J.X.; Cooper, M.A. Identification of antitubercular benzothiazinone compounds by ligand-based design. J. Med. Chem., 2012, 55(17), 7940-7944. [http://dx.doi.org/10.1021/jm3008882]. [PMID: 22916795].
[28]
Tiwari, R.; Möllmann, U.; Cho, S.; Franzblau, S.G.; Miller, P.A.; Miller, M.J. Design and syntheses of anti-tuberculosis agents inspired by BTZ043 using a scaffold simplification strategy. ACS Med. Chem. Lett., 2014, 5(5), 587-591. [http://dx.doi.org/10.1021/ ml500039g]. [PMID: 24900885].
[29]
Tiwari, R.; Miller, P.A.; Cho, S.; Franzblau, S.G.; Miller, M.J.; Miller, M.J. Syntheses and antituberculosis activity of 1,3-Benzothiazinone sulfoxide and sulfone derived from BTZ043. ACS Med. Chem. Lett., 2014, 6(2), 128-133. [http://dx.doi.org/ 10.1021/ml5003458]. [PMID: 25699139].
[30]
Tiwari, R.; Miller, P.A.; Chiarelli, L.R.; Mori, G.; Šarkan, M.; Centárová, I.; Cho, S.; Mikušová, K.; Franzblau, S.G.; Oliver, A.G.; Miller, M.J. Design, syntheses, and anti-tb activity of 1,3-benzothiazinone azide and click chemistry products inspired by BTZ043. ACS Med. Chem. Lett., 2016, 7(3), 266-270. [http://dx.doi.org/10.1021/acsmedchemlett.5b00424]. [PMID: 26985313].
[31]
Tiwari, R.; Möllmann, U.; Cho, S.; Franzblau, S.G.; Miller, P.A.; Miller, M.J. Design and syntheses of anti-tuberculosis agents inspired by BTZ043 using a scaffold simplification strategy. ACS Med. Chem. Lett., 2014, 5(5), 587-591. [http://dx.doi.org/ 10.1021/ml500039g]. [PMID: 24900885].
[32]
Peng, C.T.; Gao, C.; Wang, N.Y.; You, X.Y.; Zhang, L.D.; Zhu, Y.X.; Xv, Y.; Zuo, W.Q.; Ran, K.; Deng, H.X.; Lei, Q.; Xiao, K.J.; Yu, L.T. Synthesis and antitubercular evaluation of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives. Bioorg. Med. Chem. Lett., 2015, 25(7), 1373-1376. [http://dx.doi.org/ 10.1016/j.bmcl.2015.02.061]. [PMID: 25754492].
[33]
Chandran, M.; Renuka, J.; Sridevi, J.P.; Pedgaonkar, G.S.; Asmitha, V.; Yogeeswari, P.; Sriram, D. Benzothiazinone-piperazine derivatives as efficient Mycobacterium tuberculosis DNA gyrase inhibitors. Int. J. Mycobacteriol., 2015, 4(2), 104-115. [http://dx.doi.org/10.1016/j.ijmyco.2015.02.002]. [PMID: 26972878].
[34]
Lv, K.; You, X.; Wang, B.; Wei, Z.; Chai, Y.; Wang, B.; Wang, A.; Huang, G.; Liu, M.; Lu, Y. Identification of better pharmacokinetic benzothiazinone derivatives as new antitubercular agents. ACS Med. Chem. Lett., 2017, 8(6), 636-641. [http://dx.doi.org/ 10.1021/acsmedchemlett.7b00106]. [PMID: 28626525].
[35]
Zhang, R.; Lv, K.; Wang, B.; Li, L.; Wang, B.; Liu, M.; Guo, H.; Wang, A.; Lu, Y. Design, synthesis and antitubercular evaluation of benzothiazinones containing an oximido or amino nitrogen heterocycle moiety. RSC Advances, 2017, 7, 1480-1483. [http://dx.doi.org/10.1039/C6RA25712G].
[36]
Lv, K.; Tao, Z.; Liu, Q.; Yang, L.; Wang, B.; Wu, S.; Wang, A.; Huang, M.; Liu, M.; Lu, Y. Design, synthesis and antitubercular evaluation of benzothiazinones containing a piperidine moiety. Eur. J. Med. Chem., 2018, 151, 1-8. [http://dx.doi.org/10.1016/ j.ejmech.2018.03.060]. [PMID: 29601990].
[37]
Lu, X.; Gao, C.; Shi, Y.; Xin, T.; Rong, J.; Liu, K.; Peng, C.; Wang, N.; Lei, Q.; Zhang, Y.; Yu, L.; Wei, Y. Identification of a new series of benzothiazinone derivatives with excellent antitubercular activity and improved pharmacokinetic profiles. RSC Advances, 2018, 8, 11163-11176. [http://dx.doi.org/10.1039/ C8RA00720A].
[38]
Piton, J.; Vocat, A.; Lupien, A.; Foo, C.S.; Riabova, O.; Makarov, V.; Cole, S.T. Structure-based drug design and characterization of sulfonyl-piperazinebenzothiazinone inhibitors of DprE1 from Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 2018, 62(10), e00681-e18. [http://dx.doi.org/10.1128/AAC.00681-18]. [PMID: 30012754].
[39]
Makarov, V.; Lechartier, B.; Zhang, M.; Neres, J.; van der Sar, A.M.; Raadsen, S.A.; Hartkoorn, R.C.; Ryabova, O.B.; Vocat, A.; Decosterd, L.A.; Widmer, N.; Buclin, T.; Bitter, W.; Andries, K.; Pojer, F.; Dyson, P.J.; Cole, S.T. Towards a new combination therapy for tuberculosis with next generation benzothiazinones. EMBO Mol. Med., 2014, 6(3), 372-383. [http://dx.doi.org/ 10.1002/emmm. 201303575]. [PMID: 24500695].
[40]
Lechartier, B.; Hartkoorn, R.C.; Cole, S.T. In vitro combination studies of benzothiazinone lead compound BTZ043 against Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 2012, 56(11), 5790-5793. [http://dx.doi.org/10.1128/AAC.01476-12]. [PMID: 22926573].
[41]
Lechartier, B.; Cole, S.T. Mode of action of clofazimine and combination therapy with benzothiazinones against Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 2015, 59(8), 4457-4463. [http://dx.doi.org/10.1128/AAC.00395-15]. [PMID: 25987624].

Rights & Permissions Print Cite
Article Metrics
43
7
1
© 2024 Bentham Science Publishers | Privacy Policy