Review Article

抗菌药物抗性的新策略:DNA复制酶抑制剂

卷 26, 期 10, 2019

页: [1761 - 1787] 页: 27

弟呕挨: 10.2174/0929867324666171106160326

价格: $65

摘要

背景:所有微生物都存在抗菌药物耐药性,已成为全球健康面临的最大威胁之一。具有不同作用机制的新型抗菌药物是抗击抗生素抗性的有效武器。 目的:本综述旨在寻找可以进一步发展为临床实践的潜在药物,并为开发更有效的抗菌药物提供线索。 方法:DNA复制普遍存在于所有生物体内,是一个复杂的过程,其中涉及多种酶。细菌DNA复制起始和延伸阶段的酶为抗菌发展带来了丰富的目标,因为它们是保守和必不可少的。在这篇综述中,讨论了DNA解旋酶,DNA引物酶,拓扑异构酶,DNA聚合酶和DNA连接酶的酶抑制剂。特别关注这些酶抑制剂的结构,活性和作用方式。 结果:在这些酶中,II型拓扑异构酶是具有丰富抑制剂的最有效的靶标。对于II型拓扑异构酶抑制剂(不包括喹诺酮),NBTI和苯并咪唑脲衍生物是最有希望的抑制剂,因为它们具有良好的抗微生物活性和物理化学性质。同时,DNA促旋酶靶向药物在结核病的治疗中特别有吸引力,因为DNA促旋酶是结核分枝杆菌中唯一的II型拓扑异构酶。相对而言,利用其他DNA复制酶的抗微生物抑制剂是原始的,其中topo III的抑制剂迄今为止甚至是空白的。 结论:该综述表明DNA复制酶的抑制剂丰富,多样且前景广阔,其中许多可以开发成抗生素以应对抗生素抗性。

关键词: 抗微生物剂,抗菌素抗性,DNA复制,抑制剂,活性,作用方式。

[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.

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