Current Medicinal Chemistry

Author(s): Lanhua Yi and Xin Lü*

DOI: 10.2174/0929867324666171106160326

New Strategy on Antimicrobial-resistance: Inhibitors of DNA Replication Enzymes

Page: [1761 - 1787] Pages: 27

  • * (Excluding Mailing and Handling)

Abstract

Background: Antimicrobial resistance is found in all microorganisms and has become one of the biggest threats to global health. New antimicrobials with different action mechanisms are effective weapons to fight against antibiotic-resistance.

Objective: This review aims to find potential drugs which can be further developed into clinic practice and provide clues for developing more effective antimicrobials.

Methods: DNA replication universally exists in all living organisms and is a complicated process in which multiple enzymes are involved in. Enzymes in bacterial DNA replication of initiation and elongation phases bring abundant targets for antimicrobial development as they are conserved and indispensable. In this review, enzyme inhibitors of DNA helicase, DNA primase, topoisomerases, DNA polymerase and DNA ligase were discussed. Special attentions were paid to structures, activities and action modes of these enzyme inhibitors.

Results: Among these enzymes, type II topoisomerase is the most validated target with abundant inhibitors. For type II topoisomerase inhibitors (excluding quinolones), NBTIs and benzimidazole urea derivatives are the most promising inhibitors because of their good antimicrobial activity and physicochemical properties. Simultaneously, DNA gyrase targeted drugs are particularly attractive in the treatment of tuberculosis as DNA gyrase is the sole type II topoisomerase in Mycobacterium tuberculosis. Relatively, exploitation of antimicrobial inhibitors of the other DNA replication enzymes are primeval, in which inhibitors of topo III are even blank so far.

Conclusion: This review demonstrates that inhibitors of DNA replication enzymes are abundant, diverse and promising, many of which can be developed into antimicrobials to deal with antibioticresistance.

Keywords: Antimicrobials, antimicrobial resistance, DNA replication, inhibitors, activity, action mode.

[1]
Done, H.Y.; Venkatesan, A.K.; Halden, R.U. Does the recent growth of aquaculture create antibiotic resistance threats different from those associated with land animal production in agriculture? AAPS J., 2015, 17(3), 513-524.
[2]
Sabtu, N.; Enoch, D.A.; Brown, N.M. Antibiotic resistance: what, why, where, when and how? Br. Med. Bull., 2015, 116(1), 105-113.
[3]
Leal, J.R.; Conly, J.; Henderson, E.A.; Manns, B.J. How externalities impact an evaluation of strategies to prevent antimicrobial resistance in health care organizations. Antimicrob. Resist. Infect. Control, 2017, 6, 53.
[4]
Kohanski, M.A.; Dwyer, D.J.; Collins, J.J. How antibiotics kill bacteria: from targets to networks. Nat. Rev. Microbiol., 2010, 8(6), 423-435.
[5]
O’Donnell, M.; Langston, L.; Stillman, B. Principles and concepts of DNA replication in bacteria, archaea, and eukarya. Cold Spring Harb. Perspect. Biol., 2013, 5(7)a010108
[6]
Aldred, K.J.; Kerns, R.J.; Osheroff, N. Mechanism of quinolone action and resistance. Biochemistry, 2014, 53(10), 1565-1574.
[7]
Sanyal, G.; Doig, P. Bacterial DNA replication enzymes as targets for antibacterial drug discovery. Expert Opin. Drug Discov., 2012, 7(4), 327-339.
[8]
Mulcair, M.D.; Schaeffer, P.M.; Oakley, A.J.; Cross, H.F.; Neylon, C.; Hill, T.M.; Dixon, N.E. A molecular mousetrap determines polarity of termination of DNA replication in E. coli. Cell, 2006, 125(7), 1309-1319.
[9]
Hwang, D.S.; Kornberg, A. Opening of the replication origin of Escherichia coli by DnaA protein with protein HU or IHF. J. Biol. Chem., 1992, 267(32), 23083-23086.
[10]
Singleton, M.R.; Dillingham, M.S.; Wigley, D.B. Structure and mechanism of helicases and nucleic acid translocases. Annu. Rev. Biochem., 2007, 76, 23-50.
[11]
Lo, Y.H.; Tsai, K.L.; Sun, Y.J.; Chen, W.T.; Huang, C.Y.; Hsiao, C.D. The crystal structure of a replicative hexameric helicase DnaC and its complex with single-stranded DNA. Nucleic Acids Res., 2009, 37(3), 804-814.
[12]
Dubaele, S.; Jahnke, W.; Schoepfer, J.; Fuchs, J.; Chène, P. Inhibition of DNA helicases with DNA-competitive inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(4), 923-927.
[13]
Chino, M.; Nishikawa, K.; Umekita, M.; Hayashi, C.; Yamazaki, T.; Tsuchida, T.; Sawa, T.; Hamada, M.; Takeuchi, T. Heliquinomycin, a new inhibitor of DNA helicase, produced by Streptomyces sp. MJ929-SF2 I. Taxonomy, production, isolation, physico-chemical properties and biological activities. J. Antibiot. (Tokyo), 1996, 49(8), 752-757.
[14]
Aiello, D.; Barnes, M.H.; Biswas, E.E.; Biswas, S.B.; Gu, S.; Williams, J.D.; Bowlin, T.L.; Moir, D.T. Discovery, characterization and comparison of inhibitors of Bacillus anthracis and Staphylococcus aureus replicative DNA helicases. Bioorg. Med. Chem., 2009, 17(13), 4466-4476.
[15]
McKay, G.A.; Reddy, R.; Arhin, F.; Belley, A.; Lehoux, D.; Moeck, G.; Sarmiento, I.; Parr, T.R.; Gros, P.; Pelletier, J.; Far, A.R. Triaminotriazine DNA helicase inhibitors with antibacterial activity. Bioorg. Med. Chem. Lett., 2006, 16(5), 1286-1290.
[16]
Li, B.; Pai, R.; Aiello, D.; Di, M.; Barnes, M.H.; Peet, N.P.; Bowlin, T.L.; Moir, D.T. Optimization of a novel potent and selective bacterial DNA helicase inhibitor scaffold from a high throughput screening hit. Bioorg. Med. Chem. Lett., 2013, 23(12), 3481-3486.
[17]
Cushnie, T.P.T.; Lamb, A.J. Antimicrobial activity of flavonoids. Int. J. Antimicrob. Agents, 2005, 26(5), 343-356.
[18]
Chen, C.C.; Huang, C.Y. Inhibition of Klebsiella pneumoniae DnaB helicase by the flavonol galangin. Protein J., 2011, 30(1), 59-65.
[19]
Xu, H.; Ziegelin, G.; Schröder, W.; Frank, J.; Ayora, S.; Alonso, J.C.; Lanka, E.; Saenger, W. Flavones inhibit the hexameric replicative helicase RepA. Nucleic Acids Res., 2001, 29(24), 5058-5066.
[20]
Lin, H.H.; Huang, C.Y. Characterization of flavonol inhibition of DnaB helicase: real-time monitoring, structural modeling, and proposed mechanism. J. Biomed. Biotechnol., 2012, 2012735368
[21]
Hegde, V.R.; Pu, H.; Patel, M.; Black, T.; Soriano, A.; Zhao, W.; Gullo, V.P.; Chan, T.M. Two new bacterial DNA primase inhibitors from the plant Polygonum cuspidatum. Bioorg. Med. Chem. Lett., 2004, 14(9), 2275-2277.
[22]
Gardiner, L.; Coyle, B.J.; Chan, W.C.; Soultanas, P. Discovery of antagonist peptides against bacterial helicase-primase interaction in B. stearothermophilus by reverse yeast three-hybrid. Chem. Biol., 2005, 12(5), 595-604.
[23]
Wang, J.D.; Sanders, G.M.; Grossman, A.D. Nutritional control of elongation of DNA replication by (p)ppGpp. Cell, 2007, 128(5), 865-875.
[24]
Maciag, M.; Kochanowska, M.; Lyzeń, R.; Wegrzyn, G.; Szalewska-Pałasz, A. ppGpp inhibits the activity of Escherichia coli DnaG primase. Plasmid, 2010, 63(1), 61-67.
[25]
Kanjee, U.; Ogata, K.; Houry, W.A. Direct binding targets of the stringent response alarmone (p)ppGpp. Mol. Microbiol., 2012, 85(6), 1029-1043.
[26]
Chu, M.; Mierzwa, R.; Xu, L.; He, L.; Terracciano, J.; Patel, M.; Gullo, V.; Black, T.; Zhao, W.; Chan, T.M.; McPhail, A.T. Isolation and structure elucidation of Sch 642305, a novel bacterial DNA primase inhibitor produced by Penicillium verrucosum. J. Nat. Prod., 2003, 66(12), 1527-1530.
[27]
Agarwal, A.; Louise-May, S.; Thanassi, J.A.; Podos, S.D.; Cheng, J.; Thoma, C.; Liu, C.; Wiles, J.A.; Nelson, D.M.; Phadke, A.S.; Bradbury, B.J.; Deshpande, M.S.; Pucci, M.J. Small molecule inhibitors of E. coli primase, a novel bacterial target. Bioorg. Med. Chem. Lett., 2007, 17(10), 2807-2810.
[28]
Biswas, T.; Resto-Roldán, E.; Sawyer, S.K.; Artsimovitch, I.; Tsodikov, O.V. A novel non-radioactive primase-pyrophosphatase activity assay and its application to the discovery of inhibitors of Mycobacterium tuberculosis primase DnaG. Nucleic Acids Res., 2013, 41(4)e56
[29]
Gajadeera, C.; Willby, M.J.; Green, K.D.; Shaul, P.; Fridman, M.; Garneau-Tsodikova, S.; Posey, J.E.; Tsodikov, O.V. Antimycobacterial activity of DNA intercalator inhibitors of Mycobacterium tuberculosis primase DnaG. J. Antibiot. (Tokyo), 2015, 68(3), 153-157.
[30]
Biswas, T.; Green, K.D.; Garneau-Tsodikova, S.; Tsodikov, O.V. Discovery of inhibitors of Bacillus anthracis primase DnaG. Biochemistry, 2013, 52(39), 6905-6910.
[31]
Cheng, B.; Liu, I.F.; Tse-Dinh, Y.C. Compounds with antibacterial activity that enhance DNA cleavage by bacterial DNA topoisomerase I. J. Antimicrob. Chemother., 2007, 59(4), 640-645.
[32]
Yamaguchi, Y.; Inouye, M. An endogenous protein inhibitor, YjhX (TopAI), for topoisomerase I from Escherichia coli. Nucleic Acids Res., 2015, 43(21), 10387-10396.
[33]
Yigit, H.; Reznikoff, W.S. Escherichia coli DNA topoisomerase I copurifies with Tn5 transposase, and Tn5 transposase inhibits topoisomerase I. J. Bacteriol., 1999, 181(10), 3185-3192.
[34]
Mattenberger, Y.; Silva, F.; Belin, D. 55.2, a phage T4 ORFan gene, encodes an inhibitor of Escherichia coli topoisomerase I and increases phage fitness. PLoS One, 2015, 10(4)e0124309
[35]
Leelaram, M.N.; Bhat, A.G.; Hegde, S.M.; Manjunath, R.; Nagaraja, V. Inhibition of type IA topoisomerase by a monoclonal antibody through perturbation of DNA cleavage-religation equilibrium. FEBS J., 2012, 279(1), 55-65.
[36]
Mizushima, T.; Natori, S.; Sekimizu, K. Inhibition of Escherichia coli DNA topoisomerase I activity by phospholipids. Biochem. J., 1992, 285(Pt 2), 503-506.
[37]
Shapiro, A.B.; Newman, J.; Goteti, K.; Beaudoin, M.E.; Harrison, R.; Hopkins, S.; Agrawal, N.; Rivin, O. Improvement of the pharmacokinetics and in vivo antibacterial efficacy of a novel type IIa topoisomerase inhibitor by formulation in liposomes. Antimicrob. Agents Chemother., 2013, 57(10), 4816-4824.
[38]
Tabary, X.; Moreau, N.; Dureuil, C.; Le Goffic, F. Effect of DNA gyrase inhibitors pefloxacin, five other quinolones, novobiocin, and clorobiocin on Escherichia coli topoisomerase I. Antimicrob. Agents Chemother., 1987, 31(12), 1925-1928.
[39]
Moreau, N.J.; Robaux, H.; Baron, L.; Tabary, X. Inhibitory effects of quinolones on pro- and eucaryotic DNA topoisomerases I and II. Antimicrob. Agents Chemother., 1990, 34(10), 1955-1960.
[40]
Bansal, S.; Tawar, U.; Singh, M.; Nikravesh, A.; Good, L.; Tandon, V. Old class but new dimethoxy analogue of benzimidazole: a bacterial topoisomerase I inhibitor. Int. J. Antimicrob. Agents, 2010, 35(2), 186-190.
[41]
Bansal, S.; Sinha, D.; Singh, M.; Cheng, B.; Tse-Dinh, Y.C.; Tandon, V. 3,4-dimethoxyphenyl bis-benzimidazole, a novel DNA topoisomerase inhibitor that preferentially targets Escherichia coli topoisomerase I. J. Antimicrob. Chemother., 2012, 67(12), 2882-2891.
[42]
Ranjan, N.; Fulcrand, G.; King, A.; Brown, J.; Jiang, X.; Leng, F.; Arya, D.P. Selective inhibition of bacterial topoisomerase I by alkynyl-bisbenzimidazoles. MedChemComm, 2014, 5(6), 816-825.
[43]
Godbole, A.A.; Ahmed, W.; Bhat, R.S.; Bradley, E.K.; Ekins, S.; Nagaraja, V. Targeting Mycobacterium tuberculosis topoisomerase I by small-molecule inhibitors. Antimicrob. Agents Chemother., 2015, 59(3), 1549-1557.
[44]
Mondragón, A.; DiGate, R. The structure of Escherichia coli DNA topoisomerase III. Structure, 1999, 7(11), 1373-1383.
[45]
Changela, A.; DiGate, R.J.; Mondragón, A. Crystal structure of a complex of a type IA DNA topoisomerase with a single-stranded DNA molecule. Nature, 2001, 411(6841), 1077-1081.
[46]
Bocquet, N.; Bizard, A.H.; Abdulrahman, W.; Larsen, N.B.; Faty, M.; Cavadini, S.; Bunker, R.D.; Kowalczykowski, S.C.; Cejka, P.; Hickson, I.D.; Thomä, N.H. Structural and mechanistic insight into Holliday-junction dissolution by topoisomerase IIIα and RMI1. Nat. Struct. Mol. Biol., 2014, 21(3), 261-268.
[47]
Collin, F.; Karkare, S.; Maxwell, A. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl. Microbiol. Biotechnol., 2011, 92(3), 479-497.
[48]
Couturier, M. Bahassi el-M,Van Melderen, L. Bacterial death by DNA gyrase poisoning. Trends Microbiol., 1998, 6(7), 269-275.
[49]
Chiriac, A.I.; Kloss, F.; Krämer, J.; Vuong, C.; Hertweck, C.; Sahl, H-G. Mode of action of closthioamide: the first member of the polythioamide class of bacterial DNA gyrase inhibitors. J. Antimicrob. Chemother., 2015, 70(9), 2576-2588.
[50]
Werner, M.M.; Patel, B.A.; Talele, T.T.; Ashby, C.R.; Li, Z.; Zauhar, R.J. Dual inhibition of Staphylococcus aureus DNA gyrase and topoisomerase IV activity by phenylalanine-derived (Z)-5-arylmethylidene rhodanines. Bioorg. Med. Chem., 2015, 23(18), 6125-6137.
[51]
Schoeffler, A.J.; Berger, J.M. DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. Q. Rev. Biophys., 2008, 41(1), 41-101.
[52]
Andriole, V.T. The quinolones: past, present, and future. Clin. Infect. Dis., 2005, 41(Suppl. 2), S113-S119.
[53]
Bax, B.D.; Chan, P.F.; Eggleston, D.S.; Fosberry, A.; Gentry, D.R.; Gorrec, F.; Giordano, I.; Hann, M.M.; Hennessy, A.; Hibbs, M.; Huang, J.; Jones, E.; Jones, J.; Brown, K.K.; Lewis, C.J.; May, E.W.; Saunders, M.R.; Singh, O.; Spitzfaden, C.E.; Shen, C.; Shillings, A.; Theobald, A.J.; Wohlkonig, A.; Pearson, N.D.; Gwynn, M.N. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature, 2010, 466(7309), 935-940.
[54]
Laponogov, I.; Sohi, M.K.; Veselkov, D.A.; Pan, X-S.; Sawhney, R.; Thompson, A.W.; McAuley, K.E.; Fisher, L.M.; Sanderson, M.R. Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases. Nat. Struct. Mol. Biol., 2009, 16(6), 667-669.
[55]
Wohlkonig, A.; Chan, P.F.; Fosberry, A.P.; Homes, P.; Huang, J.; Kranz, M.; Leydon, V.R.; Miles, T.J.; Pearson, N.D.; Perera, R.L.; Shillings, A.J.; Gwynn, M.N.; Bax, B.D. Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nat. Struct. Mol. Biol., 2010, 17(9), 1152-1153.
[56]
Aldred, K.J.; McPherson, S.A.; Turnbough, C.L., Jr; Kerns, R.J.; Osheroff, N. Topoisomerase IV-quinolone interactions are mediated through a water-metal ion bridge: mechanistic basis of quinolone resistance. Nucleic Acids Res., 2013, 41(8), 4628-4639.
[57]
Mustaev, A.; Malik, M.; Zhao, X.; Kurepina, N.; Luan, G.; Oppegard, L.M.; Hiasa, H.; Marks, K.R.; Kerns, R.J.; Berger, J.M.; Drlica, K. Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding. J. Biol. Chem., 2014, 289(18), 12300-12312.
[58]
Bachurin, S.O.; Bovina, E.V.; Ustyugov, A.A. Drugs in clinical trials for Alzheimer’s Disease: the major trends. Med. Res. Rev., 2017, 37(5), 1186-1225.
[59]
Miles, T.J.; Hennessy, A.J.; Bax, B.; Brooks, G.; Brown, B.S.; Brown, P.; Cailleau, N.; Chen, D.; Dabbs, S.; Davies, D.T.; Esken, J.M.; Giordano, I.; Hoover, J.L.; Huang, J.; Jones, G.E.; Sukmar, S.K.K.; Spitzfaden, C.; Markwell, R.E.; Minthorn, E.A.; Rittenhouse, S.; Gwynn, M.N.; Pearson, N.D. Novel hydroxyl tricyclics (e.g., GSK966587) as potent inhibitors of bacterial type IIA topoisomerases. Bioorg. Med. Chem. Lett., 2013, 23(19), 5437-5441.
[60]
Wiener, J.J.M.; Gomez, L.; Venkatesan, H.; Santillán, A., Jr; Allison, B.D.; Schwarz, K.L.; Shinde, S.; Tang, L.; Hack, M.D.; Morrow, B.J.; Motley, S.T.; Goldschmidt, R.M.; Shaw, K.J.; Jones, T.K.; Grice, C.A. Tetrahydroindazole inhibitors of bacterial type II topoisomerases. Part 2: SAR development and potency against multidrug-resistant strains. Bioorg. Med. Chem. Lett., 2007, 17(10), 2718-2722.
[61]
Reck, F.; Alm, R.; Brassil, P.; Newman, J.; Dejonge, B.; Eyermann, C.J.; Breault, G.; Breen, J.; Comita-Prevoir, J.; Cronin, M.; Davis, H.; Ehmann, D.; Galullo, V.; Geng, B.; Grebe, T.; Morningstar, M.; Walker, P.; Hayter, B.; Fisher, S. Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II: broad-spectrum antibacterial agents with reduced hERG activity. J. Med. Chem., 2011, 54(22), 7834-7847.
[62]
Black, M.T.; Stachyra, T.; Platel, D.; Girard, A.M.; Claudon, M.; Bruneau, J.M.; Miossec, C. Mechanism of action of the antibiotic NXL101, a novel nonfluoroquinolone inhibitor of bacterial type II topoisomerases. Antimicrob. Agents Chemother., 2008, 52(9), 3339-3349.
[63]
Hameed, P. S.; Patil, V.; Solapure, S.; Sharma, U.; Madhavapeddi, P.; Raichurkar, A.; Chinnapattu, M.; Manjrekar, P.; Shanbhag, G.; Puttur, J.; Shinde, V.; Menasinakai, S.; Rudrapatana, S.; Achar, V.; Awasthy, D.; Nandishaiah, R.; Humnabadkar, V.; Ghosh, A.; Narayan, C.; Ramya, V.K.; Kaur, P.; Sharma, S.; Werngren, J.; Hoffner, S.; Panduga, V.; Kumar, C.N.N.; Reddy, J.; Kumar K N, M.; Ganguly, S.; Bharath, S.; Bheemarao, U.; Mukherjee, K.; Arora, U.; Gaonkar, S.; Coulson, M.; Waterson, D.; Sambandamurthy, V.K.; de Sousa, S.M. Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against Mycobacterium tuberculosis. J. Med. Chem., 2014, 57(11), 4889-4905.
[64]
Singh, S.B.; Kaelin, D.E.; Wu, J.; Miesel, L.; Tan, C.M.; Meinke, P.T.; Olsen, D.; Lagrutta, A.; Bradley, P.; Lu, J.; Patel, S.; Rickert, K.W.; Smith, R.F.; Soisson, S.; Wei, C.; Fukuda, H.; Kishii, R.; Takei, M.; Fukuda, Y. Oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad spectrum antibacterial agents. ACS Med. Chem. Lett., 2014, 5(5), 609-614.
[65]
Dougherty, T.J.; Nayar, A.; Newman, J.V.; Hopkins, S.; Stone, G.G.; Johnstone, M.; Shapiro, A.B.; Cronin, M.; Reck, F.; Ehmann, D.E. NBTI 5463 is a novel bacterial type II topoisomerase inhibitor with activity against gram-negative bacteria and in vivo efficacy. Antimicrob. Agents Chemother., 2014, 58(5), 2657-2664.
[66]
Reck, F.; Alm, R.A.; Brassil, P.; Newman, J.V.; Ciaccio, P.; McNulty, J.; Barthlow, H.; Goteti, K.; Breen, J.; Comita-Prevoir, J.; Cronin, M.; Ehmann, D.E.; Geng, B.; Godfrey, A.A.; Fisher, S.L. Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II with reduced pK(a): antibacterial agents with an improved safety profile. J. Med. Chem., 2012, 55(15), 6916-6933.
[67]
Tan, C.M.; Gill, C.J.; Wu, J.; Toussaint, N.; Yin, J.; Tsuchiya, T.; Garlisi, C.G.; Kaelin, D.; Meinke, P.T.; Miesel, L.; Olsen, D.B.; Lagrutta, A.; Fukuda, H.; Kishii, R.; Takei, M.; Oohata, K.; Takeuchi, T.; Shibue, T.; Takano, H.; Nishimura, A.; Fukuda, Y.; Singh, S.B. In vitro and in vivo characterization of the novel oxabicyclooctane-linked bacterial topoisomerase inhibitor AM-8722, a selective, potent inhibitor of bacterial DNA Gyrase. Antimicrob. Agents Chemother., 2016, 60(8), 4830-4839.
[68]
Singh, S.B.; Kaelin, D.E.; Wu, J.; Miesel, L.; Tan, C.M.; Black, T.; Nargund, R.; Meinke, P.T.; Olsen, D.B.; Lagrutta, A.; Lu, J.; Patel, S.; Rickert, K.W.; Smith, R.F.; Soisson, S.; Sherer, E.; Joyce, L.A.; Wei, C.; Peng, X.; Wang, X.; Fukuda, H.; Kishii, R.; Takei, M.; Takano, H.; Shibasaki, M.; Yajima, M.; Nishimura, A.; Shibata, T.; Fukuda, Y. Tricyclic 1,5-naphthyridinone oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents-SAR of left-hand-side moiety (Part-2). Bioorg. Med. Chem. Lett., 2015, 25(9), 1831-1835.
[69]
Singh, S.B.; Kaelin, D.E.; Wu, J.; Miesel, L.; Tan, C.M.; Gill, C.; Black, T.; Nargund, R.; Meinke, P.T.; Olsen, D.B.; Lagrutta, A.; Wei, C.; Peng, X.; Wang, X.; Fukuda, H.; Kishii, R.; Takei, M.; Takeuchi, T.; Shibue, T.; Ohata, K.; Takano, H.; Ban, S.; Nishimura, A.; Fukuda, Y. Hydroxy tricyclic 1,5-naphthyridinone oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents-SAR of RHS moiety (Part-3). Bioorg. Med. Chem. Lett., 2015, 25(12), 2473-2478.
[70]
Singh, S.B.; Kaelin, D.E.; Wu, J.; Miesel, L.; Tan, C.M.; Meinke, P.T.; Olsen, D.B.; Lagrutta, A.; Wei, C.; Peng, X.; Wang, X.; Fukuda, H.; Kishii, R.; Takei, M.; Shibata, T.; Ohata, K.; Takano, H.; Kurasaki, H.; Takeuchi, T.; Nishimura, A.; Fukuda, Y. Structure activity relationship of substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-4). Bioorg. Med. Chem. Lett., 2015, 25(11), 2409-2415.
[71]
Singh, S.B.; Kaelin, D.E.; Meinke, P.T.; Wu, J.; Miesel, L.; Tan, C.M.; Olsen, D.B.; Lagrutta, A.; Fukuda, H.; Kishii, R.; Takei, M.; Takeuchi, T.; Takano, H.; Ohata, K.; Kurasaki, H.; Nishimura, A.; Shibata, T.; Fukuda, Y. Structure activity relationship of C-2 ether substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-5). Bioorg. Med. Chem. Lett., 2015, 25(17), 3630-3635.
[72]
Singh, S.B.; Kaelin, D.E.; Wu, J.; Miesel, L.; Tan, C.M.; Meinke, P.T.; Olsen, D.B.; Lagrutta, A.; Wei, C.; Liao, Y.; Peng, X.; Wang, X.; Fukuda, H.; Kishii, R.; Takei, M.; Yajima, M.; Shibue, T.; Shibata, T.; Ohata, K.; Nishimura, A.; Fukuda, Y. Structure activity relationship of pyridoxazinone substituted RHS analogs of oxabicyclooctane-linked 1,5-naphthyridinyl novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-6). Bioorg. Med. Chem. Lett., 2015, 25(17), 3636-3643.
[73]
Singh, S.B.; Kaelin, D.E.; Wu, J.; Miesel, L.; Tan, C.M.; Meinke, P.T.; Olsen, D.B.; Lagrutta, A.; Wei, C.Q.; Liao, Y.G.; Peng, X.J.; Wang, X.; Fukuda, H.; Kishii, R.; Takei, M.; Shibata, T.; Takeuchi, T.; Ohata, K.; Nishimura, A.; Fukuda, Y. C1-C2-linker substituted 1,5-naphthyridine analogues of oxabicyclooctane-linked NBTIs as broad-spectrum antibacterial agents (part 7). MedChemComm, 2015, 6(10), 1773-1780.
[74]
Ross, J.E.; Scangarella-Oman, N.E.; Flamm, R.K.; Jones, R.N. Determination of disk diffusion and MIC quality control guidelines for GSK2140944, a novel bacterial type II topoisomerase inhibitor antimicrobial agent. J. Clin. Microbiol., 2014, 52(7), 2629-2632.
[75]
Farrell, D.J.; Sader, H.S.; Rhomberg, P.R.; Scangarella-Oman, N.E.; Flamm, R.K. In vitro activity of gepotidacin (GSK2140944) against Neisseria gonorrhoeae. Antimicrob. Agents Chemother., 2017, 61(3), e02047-e16.
[76]
O’Riordan, W.; Tiffany, C.; Scangarella-Oman, N.; Perry, C.; Hossain, M.; Ashton, T.; Dumont, E. Efficacy, safety, and tolerability of gepotidacin (GSK2140944) in the treatment of patients with suspected or confirmed gram-positive acute bacterial skin and skin structure infections. Antimicrob. Agents Chemother., 2017, 61(6), e02095-e16.
[77]
Flatman, R.H.; Howells, A.J.; Heide, L.; Fiedler, H.P.; Maxwell, A. Simocyclinone D8, an inhibitor of DNA gyrase with a novel mode of action. Antimicrob. Agents Chemother., 2005, 49(3), 1093-1100.
[78]
Edwards, M.J.; Flatman, R.H.; Mitchenall, L.A.; Stevenson, C.E.M.; Le, T.B.K.; Clarke, T.A.; McKay, A.R.; Fiedler, H-P.; Buttner, M.J.; Lawson, D.M.; Maxwell, A. A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyrase. Science, 2009, 326(5958), 1415-1418.
[79]
Bernard, P.; Couturier, M. The 41 carboxy-terminal residues of the miniF plasmid CcdA protein are sufficient to antagonize the killer activity of the CcdB protein. Mol. Gen. Genet., 1991, 226(1-2), 297-304.
[80]
Smith, A.B.; Maxwell, A. A strand-passage conformation of DNA gyrase is required to allow the bacterial toxin, CcdB, to access its binding site. Nucleic Acids Res., 2006, 34(17), 4667-4676.
[81]
Critchlow, S.E.; O’Dea, M.H.; Howells, A.J.; Couturier, M.; Gellert, M.; Maxwell, A. The interaction of the F plasmid killer protein, CcdB, with DNA gyrase: induction of DNA cleavage and blocking of transcription. J. Mol. Biol., 1997, 273(4), 826-839.
[82]
Maki, S.; Takiguchi, S.; Horiuchi, T.; Sekimizu, K.; Miki, T. Partner switching mechanisms in inactivation and rejuvenation of Escherichia coli DNA gyrase by F plasmid proteins LetD (CcdB) and LetA (CcdA). J. Mol. Biol., 1996, 256(3), 473-482.
[83]
Loris, R.; Dao-Thi, M.H.; Bahassi, E.M.; Van Melderen, L.; Poortmans, F.; Liddington, R.; Couturier, M.; Wyns, L. Crystal structure of CcdB, a topoisomerase poison from E. coli. J. Mol. Biol., 1999, 285(4), 1667-1677.
[84]
Bernard, P.; Couturier, M. Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes. J. Mol. Biol., 1992, 226(3), 735-745.
[85]
Dao-Thi, M.H.; Van Melderen, L.; De Genst, E.; Afif, H.; Buts, L.; Wyns, L.; Loris, R. Molecular basis of gyrase poisoning by the addiction toxin CcdB. J. Mol. Biol., 2005, 348(5), 1091-1102.
[86]
Trovatti, E.; Cotrim, C.A.; Garrido, S.S.; Barros, R.S.; Marchetto, R. Peptides based on CcdB protein as novel inhibitors of bacterial topoisomerases. Bioorg. Med. Chem. Lett., 2008, 18(23), 6161-6164.
[87]
Jiang, Y.; Pogliano, J.; Helinski, D.R.; Konieczny, I. ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase. Mol. Microbiol., 2002, 44(4), 971-979.
[88]
Barbosa, L.C.; Garrido, S.S.; Garcia, A.; Delfino, D.B. Santos, Ldo.N.; Marchetto, R. Design and synthesis of peptides from bacterial ParE toxin as inhibitors of topoisomerases. Eur. J. Med. Chem., 2012, 54, 591-596.
[89]
Yuan, J.; Yamaichi, Y.; Waldor, M.K. The three vibrio cholerae chromosome II-encoded ParE toxins degrade chromosome I following loss of chromosome II. J. Bacteriol., 2011, 193(3), 611-619.
[90]
Yuan, J.; Sterckx, Y.; Mitchenall, L.A.; Maxwell, A.; Loris, R.; Waldor, M.K. Vibrio cholerae ParE2 poisons DNA gyrase via a mechanism distinct from other gyrase inhibitors. J. Biol. Chem., 2010, 285(51), 40397-40408.
[91]
Manjunatha, U.H.; Maxwell, A.; Nagaraja, V. A monoclonal antibody that inhibits mycobacterial DNA gyrase by a novel mechanism. Nucleic Acids Res., 2005, 33(10), 3085-3094.
[92]
Brino, L.; Urzhumtsev, A.; Mousli, M.; Bronner, C.; Mitschler, A.; Oudet, P.; Moras, D. Dimerization of Escherichia coli DNA-gyrase B provides a structural mechanism for activating the ATPase catalytic center. J. Biol. Chem., 2000, 275(13), 9468-9475.
[93]
Bellon, S.; Parsons, J.D.; Wei, Y.; Hayakawa, K.; Swenson, L.L.; Charifson, P.S.; Lippke, J.A.; Aldape, R.; Gross, C.H. Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24 and 43 kilodaltons): a single residue dictates differences in novobiocin potency against topoisomerase IV and DNA gyrase. Antimicrob. Agents Chemother., 2004, 48(5), 1856-1864.
[94]
Oblak, M.; Kotnik, M.; Solmajer, T. Discovery and development of ATPase inhibitors of DNA gyrase as antibacterial agents. Curr. Med. Chem., 2007, 14(19), 2033-2047.
[95]
Holdgate, G.A.; Tunnicliffe, A.; Ward, W.H.J.; Weston, S.A.; Rosenbrock, G.; Barth, P.T.; Taylor, I.W.F.; Pauptit, R.A.; Timms, D. The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study. Biochemistry, 1997, 36(32), 9663-9673.
[96]
Tsai, F.T.F.; Singh, O.M.P.; Skarzynski, T.; Wonacott, A.J.; Weston, S.; Tucker, A.; Pauptit, R.A.; Breeze, A.L.; Poyser, J.P.; O’Brien, R.; Ladbury, J.E.; Wigley, D.B. The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins, 1997, 28(1), 41-52.
[97]
Lafitte, D.; Lamour, V.; Tsvetkov, P.O.; Makarov, A.A.; Klich, M.; Deprez, P.; Moras, D.; Briand, C.; Gilli, R. DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5′-methyl group of the noviose. Biochemistry, 2002, 41(23), 7217-7223.
[98]
Musicki, B.; Periers, A.M.; Laurin, P.; Ferroud, D.; Benedetti, Y.; Lachaud, S.; Chatreaux, F.; Haesslein, J.L.; Iltis, A.; Pierre, C.; Khider, J.; Tessot, N.; Airault, M.; Demassey, J.; Dupuis-Hamelin, C.; Lassaigne, P.; Bonnefoy, A.; Vicat, P.; Klich, M. Improved antibacterial activities of coumarin antibiotics bearing 5′,5′-dialkylnoviose: biological activity of RU79115. Bioorg. Med. Chem. Lett., 2000, 10(15), 1695-1699.
[99]
Kamiyama, T.; Shimma, N.; Ohtsuka, T.; Nakayama, N.; Itezono, Y.; Nakada, N.; Watanabe, J.; Yokose, K. Cyclothialidine, a novel DNA gyrase inhibitor. II. Isolation, characterization and structure elucidation. J. Antibiot. (Tokyo), 1994, 47(1), 37-45.
[100]
Lewis, R.J.; Singh, O.M.P.; Smith, C.V.; Skarzynski, T.; Maxwell, A.; Wonacott, A.J.; Wigley, D.B. The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography. EMBO J., 1996, 15(6), 1412-1420.
[101]
Goetschi, E.; Angehrn, P.; Gmuender, H.; Hebeisen, P.; Link, H.; Masciadri, R.; Nielsen, J. Cyclothialidine and its congeners: a new class of DNA gyrase inhibitors. Pharmacol. Ther., 1993, 60(2), 367-380.
[102]
Angehrn, P.; Buchmann, S.; Funk, C.; Goetschi, E.; Gmuender, H.; Hebeisen, P.; Kostrewa, D.; Link, H.; Luebbers, T.; Masciadri, R.; Nielsen, J.; Reindl, P.; Ricklin, F.; Schmitt-Hoffmann, A.; Theil, F.P. New antibacterial agents derived from the DNA gyrase inhibitor cyclothialidine. J. Med. Chem., 2004, 47(6), 1487-1513.
[103]
Rudolph, J.; Theis, H.; Hanke, R.; Endermann, R.; Johannsen, L.; Geschke, F. seco-Cyclothialidines: new concise synthesis, inhibitory activity toward bacterial and human DNA topoisomerases, and antibacterial properties. J. Med. Chem., 2001, 44(4), 619-626.
[104]
Angehrn, P.; Goetschi, E.; Gmuender, H.; Hebeisen, P.; Hennig, M.; Kuhn, B.; Luebbers, T.; Reindl, P.; Ricklin, F.; Schmitt-Hoffmann, A. A new DNA gyrase inhibitor subclass of the cyclothialidine family based on a bicyclic dilactam-lactone scaffold. Synthesis and antibacterial properties. J. Med. Chem., 2011, 54(7), 2207-2224.
[105]
Fang, Y.; Lu, Y.; Zang, X.; Wu, T.; Qi, X.; Pan, S.; Xu, X. 3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors. Scientific Reports, 2016, 6(23634), Article No.: 23634.
[106]
Plaper, A.; Golob, M.; Hafner, I.; Oblak, M.; Solmajer, T.; Jerala, R. Characterization of quercetin binding site on DNA gyrase. Biochem. Biophys. Res. Commun., 2003, 306(2), 530-536.
[107]
Suriyanarayanan, B.; Shanmugam, K.; Santhosh, R.S. Synthetic quercetin inhibits mycobacterial growth possibly by interacting with DNA gyrase. Rom. Biotechnol. Lett., 2013, 18(5), 8587-8593.
[108]
Hossion, A.M.L.; Zamami, Y.; Kandahary, R.K.; Tsuchiya, T.; Ogawa, W.; Iwado, A.; Sasaki, K. Quercetin diacylglycoside analogues showing dual inhibition of DNA gyrase and topoisomerase IV as novel antibacterial agents. J. Med. Chem., 2011, 54(11), 3686-3703.
[109]
Phillips, J.W.; Goetz, M.A.; Smith, S.K.; Zink, D.L.; Polishook, J.; Onishi, R.; Salowe, S.; Wiltsie, J.; Allocco, J.; Sigmund, J.; Dorso, K.; Lee, S.; Skwish, S.; de la Cruz, M.; Martín, J.; Vicente, F.; Genilloud, O.; Lu, J.; Painter, R.E.; Young, K.; Overbye, K.; Donald, R.G.K.; Singh, S.B. Discovery of kibdelomycin, a potent new class of bacterial type II topoisomerase inhibitor by chemical-genetic profiling in Staphylococcus aureus. Chem. Biol., 2011, 18(8), 955-965.
[110]
Lu, J.; Patel, S.; Sharma, N.; Soisson, S.M.; Kishii, R.; Takei, M.; Fukuda, Y.; Lumb, K.J.; Singh, S.B. Structures of kibdelomycin bound to Staphylococcus aureus GyrB and ParE showed a novel U-shaped binding mode. ACS Chem. Biol., 2014, 9(9), 2023-2031.
[111]
Singh, S.B.; Dayananth, P.; Balibar, C.J.; Garlisi, C.G.; Lu, J.; Kishii, R.; Takei, M.; Fukuda, Y.; Ha, S.; Young, K. Kibdelomycin is a bactericidal broad-spectrum aerobic antibacterial agent. Antimicrob. Agents Chemother., 2015, 59(6), 3474-3481.
[112]
Singh, S.B.; Goetz, M.A.; Smith, S.K.; Zink, D.L.; Polishook, J.; Onishi, R.; Salowe, S.; Wiltsie, J.; Allocco, J.; Sigmund, J.; Dorso, K.; de la Cruz, M.; Martín, J.; Vicente, F.; Genilloud, O.; Donald, R.G.; Phillips, J.W. Kibdelomycin A, a congener of kibdelomycin, derivatives and their antibacterial activities. Bioorg. Med. Chem. Lett., 2012, 22(23), 7127-7130.
[113]
Garcia-Pino, A.; Zenkin, N.; Loris, R. The many faces of Fic: structural and functional aspects of Fic enzymes. Trends Biochem. Sci., 2014, 39(3), 121-129.
[114]
Harms, A.; Stanger, F.V.; Scheu, P.D.; de Jong, I.G.; Goepfert, A.; Glatter, T.; Gerdes, K.; Schirmer, T.; Dehio, C. Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA Topology. Cell Rep., 2015, 12(9), 1497-1507.
[115]
Lu, C.; Nakayasu, E.S.; Zhang, L-Q.; Luo, Z-Q. Identification of Fic-1 as an enzyme that inhibits bacterial DNA replication by AMPylating GyrB, promoting filament formation. Sci. Signal., 2016, 9(412), ra11.
[116]
Paneth, A.; Stączek, P.; Plech, T.; Strzelczyk, A.; Dzitko, K.; Wujec, M.; Kuśmierz, E.; Kosikowska, U.; Grzegorczyk, A.; Paneth, P. Biological evaluation and molecular modelling study of thiosemicarbazide derivatives as bacterial type IIA topoisomerases inhibitors. J. Enzyme Inhib. Med. Chem., 2016, 31(1), 14-22.
[117]
Jeankumar, V.U.; Saxena, S.; Vats, R.; Reshma, R.S.; Janupally, R.; Kulkarni, P.; Yogeeswari, P.; Sriram, D. Structure-guided discovery of antitubercular agents that target the gyrase ATPase domain. ChemMedChem, 2016, 11(5), 539-548.
[118]
Tomašič, T.; Katsamakas, S.; Hodnik, Ž.; Ilaš, J.; Brvar, M.; Solmajer, T.; Montalvão, S.; Tammela, P.; Banjanac, M.; Ergović, G.; Anderluh, M.; Peterlin Mašič, L.; Kikelj, D. Discovery of 4,5,6,7-Tetrahydrobenzo [1,2-d]thiazoles as novel DNA gyrase inhibitors targeting the ATP-binding Site. J. Med. Chem., 2015, 58(14), 5501-5521.
[119]
Jeankumar, V.U.; Renuka, J.; Santosh, P.; Soni, V.; Sridevi, J.P.; Suryadevara, P.; Yogeeswari, P.; Sriram, D. Thiazole-aminopiperidine hybrid analogues: design and synthesis of novel Mycobacterium tuberculosis GyrB inhibitors. Eur. J. Med. Chem., 2013, 70, 143-153.
[120]
Brvar, M.; Perdih, A.; Hodnik, V.; Renko, M.; Anderluh, G.; Jerala, R.; Solmajer, T. In silico discovery and biophysical evaluation of novel 5-(2-hydroxybenzylidene) rhodanine inhibitors of DNA gyrase B. Bioorg. Med. Chem., 2012, 20(8), 2572-2580.
[121]
Tanitame, A.; Oyamada, Y.; Ofuji, K.; Fujimoto, M.; Suzuki, K.; Ueda, T.; Terauchi, H.; Kawasaki, M.; Nagai, K.; Wachi, M.; Yamagishi, J. Synthesis and antibacterial activity of novel and potent DNA gyrase inhibitors with azole ring. Bioorg. Med. Chem., 2004, 12(21), 5515-5524.
[122]
Tanitame, A.; Oyamada, Y.; Ofuji, K.; Kyoya, Y.; Suzuki, K.; Ito, H.; Kawasaki, M.; Nagai, K.; Wachi, M.; Yamagishi, J. Design, synthesis and structure-activity relationship studies of novel indazole analogues as DNA gyrase inhibitors with Gram-positive antibacterial activity. Bioorg. Med. Chem. Lett., 2004, 14(11), 2857-2862.
[123]
Jeankumar, V.U.; Kotagiri, S.; Janupally, R.; Suryadevara, P.; Sridevi, J.P.; Medishetti, R.; Kulkarni, P.; Yogeeswari, P.; Sriram, D. Exploring the gyrase ATPase domain for tailoring newer anti-tubercular drugs: hit to lead optimization of a novel class of thiazole inhibitors. Bioorg. Med. Chem., 2015, 23(3), 588-601.
[124]
Tanitame, A.; Oyamada, Y.; Ofuji, K.; Fujimoto, M.; Iwai, N.; Hiyama, Y.; Suzuki, K.; Ito, H.; Terauchi, H.; Kawasaki, M.; Nagai, K.; Wachi, M.; Yamagishi, J. Synthesis and antibacterial activity of a novel series of potent DNA gyrase inhibitors. Pyrazole derivatives. J. Med. Chem., 2004, 47(14), 3693-3696.
[125]
Poyser, J.P.; Telford, B.; Timms, D.; Block, M.H.; Hales, N.J. Triazine derivatives and their use as antibacterial agents U.S. Patent, WO1999001442A1, Jan 14, 1999.
[126]
Sherer, B.A.; Hull, K.; Green, O.; Basarab, G.; Hauck, S.; Hill, P.; Loch, J.T., III; Mullen, G.; Bist, S.; Bryant, J.; Boriack-Sjodin, A.; Read, J.; DeGrace, N.; Uria-Nickelsen, M.; Illingworth, R.N.; Eakin, A.E. Pyrrolamide DNA gyrase inhibitors: optimization of antibacterial activity and efficacy. Bioorg. Med. Chem. Lett., 2011, 21(24), 7416-7420.
[127]
Kale, M.G.; Raichurkar, A. P, S.H.; Waterson, D.; McKinney, D.; Manjunatha, M.R.; Kranthi, U.; Koushik, K.; Jena, Lk.; Shinde, V.; Rudrapatna, S.; Barde, S.; Humnabadkar, V.; Madhavapeddi, P.; Basavarajappa, H.; Ghosh, A.; Ramya, V.K.; Guptha, S.; Sharma, S.; Vachaspati, P.; Kumar, K.N.M.; Giridhar, J.; Reddy, J.; Panduga, V.; Ganguly, S.; Ahuja, V.; Gaonkar, S.; Kumar, C.N.N.; Ogg, D.; Tucker, J.A.; Boriack-Sjodin, P.A.; de Sousa, S.M.; Sambandamurthy, V.K.; Ghorpade, S.R. Thiazolopyridine ureas as novel antitubercular agents acting through inhibition of DNA Gyrase B. J. Med. Chem., 2013, 56(21), 8834-8848.
[128]
Hill, P.; Manchester, J.; Laura, E.P. Heterocyclic urea derivatives for the treatment of bacterial infections U.S. Patent, WO2009147433A1, Dec 10, 2009
[129]
Starr, J.T.; Sciotti, R.J.; Hanna, D.L.; Huband, M.D.; Mullins, L.M.; Cai, H.; Gage, J.W.; Lockard, M.; Rauckhorst, M.R.; Owen, R.M.; Lall, M.S.; Tomilo, M.; Chen, H.; McCurdy, S.P.; Barbachyn, M.R. 5-(2-Pyrimidinyl)-imidazo [1,2-a]pyridines are antibacterial agents targeting the ATPase domains of DNA gyrase and topoisomerase IV. Bioorg. Med. Chem. Lett., 2009, 19(18), 5302-5306.
[130]
Ghorpade, S.R.; Kale, M.G.; Mckinney, D.C.; Peer Mohamed, S.H.; Raichurkar, A.K.V. Thiazolo [5, 4-b] pyridine and oxazolo [5, 4-b] pyridine derivatives as antibacterial agents U.S. Patent, WO2009GB50609, Dec 10, 2009.
[131]
Sattigeri, J. Benzothiazoles and aza-analogues thereof use as antibacterial agents U.S, WO2009156966A1, Dec 30;2009
[132]
Charifson, P.S.; Grillot, A-L.; Grossman, T.H.; Parsons, J.D.; Badia, M.; Bellon, S.; Deininger, D.D.; Drumm, J.E.; Gross, C.H.; LeTiran, A.; Liao, Y.; Mani, N.; Nicolau, D.P.; Perola, E.; Ronkin, S.; Shannon, D.; Swenson, L.L.; Tang, Q.; Tessier, P.R.; Tian, S-K.; Trudeau, M.; Wang, T.; Wei, Y.; Zhang, H.; Stamos, D. Novel dual-targeting benzimidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent antibacterial activity: intelligent design and evolution through the judicious use of structure-guided design and structure-activity relationships. J. Med. Chem., 2008, 51(17), 5243-5263.
[133]
Tari, L.W.; Trzoss, M.; Bensen, D.C.; Li, X.; Chen, Z.; Lam, T.; Zhang, J.; Creighton, C.J.; Cunningham, M.L.; Kwan, B.; Stidham, M.; Shaw, K.J.; Lightstone, F.C.; Wong, S.E.; Nguyen, T.B.; Nix, J.; Finn, J. Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity. Bioorg. Med. Chem. Lett., 2013, 23(5), 1529-1536.
[134]
Tari, L.W.; Li, X.; Trzoss, M.; Bensen, D.C.; Chen, Z.; Lam, T.; Zhang, J.; Lee, S.J.; Hough, G.; Phillipson, D.; Akers-Rodriguez, S.; Cunningham, M.L.; Kwan, B.P.; Nelson, K.J.; Castellano, A.; Locke, J.B.; Brown-Driver, V.; Murphy, T.M.; Ong, V.S.; Pillar, C.M.; Shinabarger, D.L.; Nix, J.; Lightstone, F.C.; Wong, S.E.; Nguyen, T.B.; Shaw, K.J.; Finn, J. Tricyclic GyrB/ParE (TriBE) inhibitors: a new class of broad-spectrum dual-targeting antibacterial agents. PLoS One, 2013, 8(12)e84409
[135]
Grillot, A.L.; Le Tiran, A.; Shannon, D.; Krueger, E.; Liao, Y.; O’Dowd, H.; Tang, Q.; Ronkin, S.; Wang, T.; Waal, N.; Li, P.; Lauffer, D.; Sizensky, E.; Tanoury, J.; Perola, E.; Grossman, T.H.; Doyle, T.; Hanzelka, B.; Jones, S.; Dixit, V.; Ewing, N.; Liao, S.; Boucher, B.; Jacobs, M.; Bennani, Y.; Charifson, P.S. Second-generation antibacterial benzimidazole ureas: discovery of a preclinical candidate with reduced metabolic liability. J. Med. Chem., 2014, 57(21), 8792-8816.
[136]
Charifson, P.S.; Grillot, A.L.; Grossman, T.H.; Parsons, J.D.; Badia, M.; Bellon, S.; Deininger, D.D.; Drumm, J.E.; Gross, C.H.; LeTiran, A.; Liao, Y.; Mani, N.; Nicolau, D.P.; Perola, E.; Ronkin, S.; Shannon, D.; Swenson, L.L.; Tang, Q.; Tessier, P.R.; Tian, S.K.; Trudeau, M.; Wang, T.; Wei, Y.; Zhang, H.; Stamos, D. Novel dual-targeting benzimidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent antibacterial activity: intelligent design and evolution through the judicious use of structure-guided design and structure-activity relationships. J. Med. Chem., 2008, 51(17), 5243-5263.
[137]
O’Dowd, H.; Shannon, D.E.; Chandupatla, K.R.; Dixit, V.; Engtrakul, J.J.; Ye, Z.; Jones, S.M.; O’Brien, C.F.; Nicolau, D.P.; Tessier, P.R.; Crandon, J.L.; Song, B.; Macikenas, D.; Hanzelka, B.L.; Le Tiran, A.; Bennani, Y.L.; Charifson, P.S.; Grillot, A.L. Discovery and characterization of a water-soluble prodrug of a dual inhibitor of bacterial DNA gyrase and topoisomerase IV. ACS Med. Chem. Lett., 2015, 6(7), 822-826.
[138]
Kelman, Z.; O’Donnell, M. DNA polymerase III holoenzyme: structure and function of a chromosomal replicating machine. Annu. Rev. Biochem., 1995, 64(1), 171-200.
[139]
Tougu, K.; Marians, K.J. The interaction between helicase and primase sets the replication fork clock. J. Biol. Chem., 1996, 271(35), 21398-21405.
[140]
Daly, J.S.; Giehl, T.J.; Brown, N.C.; Zhi, C.; Wright, G.E.; Ellison, R.T., III In vitro antimicrobial activities of novel anilinouracils which selectively inhibit DNA polymerase III of gram-positive bacteria. Antimicrob. Agents Chemother., 2000, 44(8), 2217-2221.
[141]
Low, R.L.; Rashbaum, S.A.; Cozzarelli, N.R. Mechanism of inhibition of Bacillus subtilis DNA polymerase 3 by the arylhydrazinopyrimidine antimicrobial agents. Proc. Natl. Acad. Sci. USA, 1974, 71(8), 2973-2977.
[142]
Mackenzie, J.M.; Neville, M.M.; Wright, G.E.; Brown, N.C. Hydroxyphenylazopyrimidines: characterization of the active forms and their inhibitory action on a DNA polymerase from Bacillus subtilis. Proc. Natl. Acad. Sci. USA, 1973, 70(2), 512-516.
[143]
Zhi, C.; Long, Z.Y.; Manikowski, A.; Brown, N.C.; Tarantino, P.M., Jr; Holm, K.; Dix, E.J.; Wright, G.E.; Foster, K.A.; Butler, M.M.; LaMarr, W.A.; Skow, D.J.; Motorina, I.; Lamothe, S.; Storer, R. Synthesis and antibacterial activity of 3-substituted-6-(3-ethyl-4-methylanilino)uracils. J. Med. Chem., 2005, 48(22), 7063-7074.
[144]
Tarantino, P.M., Jr; Zhi, C.; Wright, G.E.; Brown, N.C. Inhibitors of DNA polymerase III as novel antimicrobial agents against gram-positive eubacteria. Antimicrob. Agents Chemother., 1999, 43(8), 1982-1987.
[145]
Rose, Y.; Ciblat, S.; Reddy, R.; Belley, A.C.; Dietrich, E.; Lehoux, D.; McKay, G.A.; Poirier, H.; Far, A.R.; Delorme, D. Novel non-nucleobase inhibitors of Staphylococcus aureus DNA polymerase IIIC. Bioorg. Med. Chem. Lett., 2006, 16(4), 891-896.
[146]
Xu, W.C.; Wright, G.E.; Brown, N.C.; Long, Z.Y.; Zhi, C.X.; Dvoskin, S.; Gambino, J.J.; Barnes, M.H.; Butler, M.M. 7-Alkyl-N(2)-substituted-3-deazaguanines. Synthesis, DNA polymerase III inhibition and antibacterial activity. Bioorg. Med. Chem. Lett., 2011, 21(14), 4197-4202.
[147]
Zhi, C.; Long, Z.Y.; Manikowski, A.; Comstock, J.; Xu, W.C.; Brown, N.C.; Tarantino, P.M., Jr; Holm, K.A.; Dix, E.J.; Wright, G.E.; Barnes, M.H.; Butler, M.M.; Foster, K.A.; LaMarr, W.A.; Bachand, B.; Bethell, R.; Cadilhac, C.; Charron, S.; Lamothe, S.; Motorina, I.; Storer, R. Hybrid antibacterials. DNA polymerase-topoisomerase inhibitors. J. Med. Chem., 2006, 49(4), 1455-1465.
[148]
Butler, M.M.; Lamarr, W.A.; Foster, K.A.; Barnes, M.H.; Skow, D.J.; Lyden, P.T.; Kustigian, L.M.; Zhi, C.; Brown, N.C.; Wright, G.E.; Bowlin, T.L. Antibacterial activity and mechanism of action of a novel anilinouracil-fluoroquinolone hybrid compound. Antimicrob. Agents Chemother., 2007, 51(1), 119-127.
[149]
Butler, M.M. Antibacterial pyrazole carboxylic acid hydrazides U.S. Patent, WO2004094370, Nov 4, 2004.
[150]
Guiles, J.; Sun, X.; Critchley, I.A.; Ochsner, U.; Tregay, M.; Stone, K.; Bertino, J.; Green, L.; Sabin, R.; Dean, F.; Dallmann, H.G.; McHenry, C.S.; Janjic, N. Quinazolin-2-ylamino-quinazolin-4-ols as novel non-nucleoside inhibitors of bacterial DNA polymerase III. Bioorg. Med. Chem. Lett., 2009, 19(3), 800-802.
[151]
Barnes, M.H.; Butler, M.M.; Wright, G.E.; Brown, N.C. Antimicrobials targeted to the replication-specific DNA polymerases of gram-positive bacteria: target potential of dnaE. Infect. Disord. Drug Targets, 2012, 12(5), 327-331.
[152]
Painter, R.E.; Adam, G.C.; Arocho, M.; DiNunzio, E.; Donald, R.G.K.; Dorso, K.; Genilloud, O.; Gill, C.; Goetz, M.; Hairston, N.N.; Murgolo, N.; Nare, B.; Olsen, D.B.; Powles, M.; Racine, F.; Su, J.; Vicente, F.; Wisniewski, D.; Xiao, L.; Hammond, M.; Young, K. Elucidation of DnaE as the Antibacterial Target of the Natural Product, Nargenicin. Chem. Biol., 2015, 22(10), 1362-1373.
[153]
Dwivedi, N.; Dube, D.; Pandey, J.; Singh, B.; Kukshal, V.; Ramachandran, R.; Tripathi, R.P. NAD(+)-dependent DNA ligase: a novel target waiting for the right inhibitor. Med. Res. Rev., 2008, 28(4), 545-568.
[154]
Srivastava, S.K.; Dube, D.; Tewari, N.; Dwivedi, N.; Tripathi, R.P.; Ramachandran, R. Mycobacterium tuberculosis NAD+-dependent DNA ligase is selectively inhibited by glycosylamines compared with human DNA ligase I. Nucleic Acids Res., 2005, 33(22), 7090-7101.
[155]
Gu, W.; Wang, T.; Maltais, F.; Ledford, B.; Kennedy, J.; Wei, Y.; Gross, C.H.; Parsons, J.; Duncan, L.; Arends, S.J.R.; Moody, C.; Perola, E.; Green, J.; Charifson, P.S. Design, synthesis and biological evaluation of potent NAD+-dependent DNA ligase inhibitors as potential antibacterial agents. Part I: aminoalkoxypyrimidine carboxamides. Bioorg. Med. Chem. Lett., 2012, 22(11), 3693-3698.
[156]
Srivastava, S.K.; Tripathi, R.P.; Ramachandran, R. NAD+-dependent DNA Ligase (Rv3014c) from Mycobacterium tuberculosis. Crystal structure of the adenylation domain and identification of novel inhibitors. J. Biol. Chem., 2005, 280(34), 30273-30281.
[157]
Brötz-Oesterhelt, H.; Knezevic, I.; Bartel, S.; Lampe, T.; Warnecke-Eberz, U.; Ziegelbauer, K.; Häbich, D.; Labischinski, H. Specific and potent inhibition of NAD+-dependent DNA ligase by pyridochromanones. J. Biol. Chem., 2003, 278(41), 39435-39442.
[158]
Srivastava, S.K.; Dube, D.; Kukshal, V.; Jha, A.K.; Hajela, K.; Ramachandran, R. NAD+-dependent DNA ligase (Rv3014c) from Mycobacterium tuberculosis: novel structure-function relationship and identification of a specific inhibitor. Proteins, 2007, 69(1), 97-111.
[159]
Meier, T.I.; Yan, D.; Peery, R.B.; McAllister, K.A.; Zook, C.; Peng, S.B.; Zhao, G. Identification and characterization of an inhibitor specific to bacterial NAD+-dependent DNA ligases. FEBS J., 2008, 275(21), 5258-5271.
[160]
Kukshal, V.; Mishra, M.; Ajay, A.; Khanam, T.; Sharma, R.; Dube, D.; Chopra, D.; Tripathi, R.P.; Ramachandran, R. Synthesis and bioevaluation of aryl hydroxamates distinguishing between NAD(+) and ATP-dependent DNA ligases. MedChemComm, 2012, 3(4), 453-461.
[161]
Miesel, L.; Kravec, C.; Xin, A.T.P.; McMonagle, P.; Ma, S.; Pichardo, J.; Feld, B.; Barrabee, E.; Palermo, R. A high-throughput assay for the adenylation reaction of bacterial DNA ligase. Anal. Biochem., 2007, 366(1), 9-17.
[162]
Mills, S.D.; Eakin, A.E.; Buurman, E.T.; Newman, J.V.; Gao, N.; Huynh, H.; Johnson, K.D.; Lahiri, S.; Shapiro, A.B.; Walkup, G.K.; Yang, W.; Stokes, S.S.; Novel Bacterial, N.A.D. Novel bacterial NAD+-dependent DNA ligase inhibitors with broad-spectrum activity and antibacterial efficacy in vivo. Antimicrob. Agents Chemother., 2011, 55(3), 1088-1096.
[163]
Jahić, H.; Liu, C.F.; Thresher, J.; Livchak, S.; Wang, H.; Ehmann, D.E. The kinetic mechanism of S. pneumoniae DNA ligase and inhibition by adenosine-based antibacterial compounds. Biochem. Pharmacol., 2012, 84(5), 654-660.
[164]
Stokes, S.S.; Huynh, H.; Gowravaram, M.; Albert, R.; Cavero-Tomas, M.; Chen, B.; Harang, J.; Loch, J.T., III; Lu, M.; Mullen, G.B.; Zhao, S.; Liu, C-F.; Mills, S.D. Discovery of bacterial NAD+-dependent DNA ligase inhibitors: optimization of antibacterial activity. Bioorg. Med. Chem. Lett., 2011, 21(15), 4556-4560.
[165]
Stokes, S.S.; Gowravaram, M.; Huynh, H.; Lu, M.; Mullen, G.B.; Chen, B.; Albert, R.; O’Shea, T.J.; Rooney, M.T.; Hu, H.; Newman, J.V.; Mills, S.D. Discovery of bacterial NAD+-dependent DNA ligase inhibitors: improvements in clearance of adenosine series. Bioorg. Med. Chem. Lett., 2012, 22(1), 85-89.
[166]
Murphy-Benenato, K.; Wang, H.; McGuire, H.M.; Davis, H.E.; Gao, N.; Prince, D.B.; Jahic, H.; Stokes, S.S.; Boriack-Sjodin, P.A. Identification through structure-based methods of a bacterial NAD(+)-dependent DNA ligase inhibitor that avoids known resistance mutations. Bioorg. Med. Chem. Lett., 2014, 24(1), 360-366.
[167]
Wang, T.; Duncan, L.; Gu, W.; O’Dowd, H.; Wei, Y.; Perola, E.; Parsons, J.; Gross, C.H.; Moody, C.S.; Arends, S.J.R.; Charifson, P.S. Design, synthesis and biological evaluation of potent NAD+-dependent DNA ligase inhibitors as potential antibacterial agents. Part 2: 4-amino-pyrido [2,3-d]pyrimidin-5(8H)-ones. Bioorg. Med. Chem. Lett., 2012, 22(11), 3699-3703.
[168]
Surivet, J-P.; Lange, R.; Hubschwerlen, C.; Keck, W.; Specklin, J-L.; Ritz, D.; Bur, D.; Locher, H.; Seiler, P.; Strasser, D.S.; Prade, L.; Kohl, C.; Schmitt, C.; Chapoux, G.; Ilhan, E.; Ekambaram, N.; Athanasiou, A.; Knezevic, A.; Sabato, D.; Chambovey, A.; Gaertner, M.; Enderlin, M.; Boehme, M.; Sippel, V.; Wyss, P. Structure-guided design, synthesis and biological evaluation of novel DNA ligase inhibitors with in vitro and in vivo anti-staphylococcal activity. Bioorg. Med. Chem. Lett., 2012, 22(21), 6705-6711.