Monobactams: A Unique Natural Scaffold of Four-Membered Ring Skeleton, Recent Development to Clinically Overcome Infections by Multidrug- Resistant Microbes

Boucher, H.W.; Talbot, G.H.; Benjamin, D.K., Jr; Bradley, J.; Guidos, R.J.; Jones, R.N.; Murray, B.E.; Bonomo, R.A.; Gilbert, D. 10 x ’20 Progress-development of new drugs active against gram-negative bacilli: An update from the Infectious Diseases Society of America. Clin. Infect. Dis., 2013, 56(12), 1685-1694.
[http://dx.doi.org/10.1093/cid/cit152] [PMID: 23599308]

Spellberg, B.; Shlaes, D. Prioritized current unmet needs for antibacterial therapies. Clin. Pharmacol. Ther., 2014, 96(2), 151-153.
[http://dx.doi.org/10.1038/clpt.2014.106] [PMID: 25056396]

Li, B.; Yi, Y.; Wang, Q.; Woo, P.C.; Tan, L.; Jing, H.; Gao, G.F.; Liu, C.H. Analysis of drug resistance determinants in Klebsiella pneumoniae isolates from a tertiary-care hospital in Beijing, China. PLoS One, 2012, 7(7)e42280
[http://dx.doi.org/10.1371/journal.pone.0042280] [PMID: 22860106]

Giske, C.G.; Monnet, D.L.; Cars, O.; Carmeli, Y. Clinical and economic impact of common multidrug-resistant gram-negative bacilli. Antimicrob. Agents Chemother., 2008, 52(3), 813-821.
[http://dx.doi.org/10.1128/AAC.01169-07] [PMID: 18070961]

Sykes, R.B.; Bonner, D.P. Aztreonam: The first monobactam. Am. J. Med., 1985, 78(2A), 2-10.
[http://dx.doi.org/10.1016/0002-9343(85)90196-2] [PMID: 3871589]

Alván, G.; Nord, C.E. Adverse effects of monobactams and carbapenems. Drug Saf., 1995, 12(5), 305-313.
[http://dx.doi.org/10.2165/00002018-199512050-00003] [PMID: 7669260]

Decuyper, L.; Jukič, M.; Sosič, I.; Žula, A.; D’hooghe, M.; Gobec, S. Antibacterial and beta-Lactamase inhibitory activity of monocyclic beta-lactams. Med. Res. Rev., 2018, 38(2), 426-503.
[http://dx.doi.org/10.1002/med.21443] [PMID: 28815732]

Tan, L.; Tao, Y.; Wang, T.; Zou, F.; Zhang, S.; Kou, Q.; Niu, A.; Chen, Q.; Chu, W.; Chen, X.; Wang, H.; Yang, Y. Discovery of novel pyridone-conjugated monosulfactams as potent and broad-spectrum antibiotics for multidrug-resistant gram-negative infections. J. Med. Chem., 2017, 60(7), 2669-2684.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01261] [PMID: 28287720]

Reck, F.; Bermingham, A.; Blais, J.; Capka, V.; Cariaga, T.; Casarez, A.; Colvin, R.; Dean, C.R.; Fekete, A.; Gong, W.; Growcott, E.; Guo, H.; Jones, A.K.; Li, C.; Li, F.; Lin, X.; Lindvall, M.; Lopez, S.; McKenney, D.; Metzger, L.; Moser, H.E.; Prathapam, R.; Rasper, D.; Rudewicz, P.; Sethuraman, V.; Shen, X.; Shaul, J.; Simmons, R.L.; Tashiro, K.; Tang, D.; Tjandra, M.; Turner, N.; Uehara, T.; Vitt, C.; Whitebread, S.; Yifru, A.; Zang, X.; Zhu, Q. Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae - Identification of LYS228. Bioorg. Med. Chem. Lett., 2018, 28(4), 748-755.
[http://dx.doi.org/10.1016/j.bmcl.2018.01.006] [PMID: 29336873]

Khan, A.U.; Maryam, L.; Zarrilli, R. Structure, genetics and worldwide spread of New Delhi metallo-beta-lactamase (NDM): A threat to public health. BMC Microbiol., 2017, 17(1), 101.

Kou, Q.; Wang, T.; Zou, F.; Zhang, S.; Chen, Q.; Yang, Y. Design, synthesis and biological evaluation of C(4) substituted monobactams as antibacterial agents against multidrug-resistant Gram-negative bacteria. Eur. J. Med. Chem., 2018, 151, 98-109.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.058] [PMID: 29605810]

Lall, M.S.; Tao, Y.; Arcari, J.T.; Boyles, D.C.; Brown, M.F.; Damon, D.B.; Lilley, S.C.; Mitton-Fry, M.J.; Starr, J.; Stewart, A.M.; Sun, J. Process development for the synthesis of monocyclic β-Lactam Core 17. Org. Process Res. Dev., 2018, 22(2), 212-218.
[http://dx.doi.org/10.1021/acs.oprd.7b00359]

Horsman, M.E.; Marous, D.R.; Li, R.; Oliver, R.A.; Byun, B.; Emrich, S.J.; Boggess, B.; Townsend, C.A.; Mobashery, S. Whole-genome shotgun sequencing of two beta-proteobacterial species in search of the bulgecin biosynthetic cluster. ACS Chem. Biol., 2017, 12(10), 2552-2557.
[http://dx.doi.org/10.1021/acschembio.7b00687] [PMID: 28937735]

Oliver, R.A.; Li, R.; Townsend, C.A. Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase. Nat. Chem. Biol., 2018, 14(1), 5-7.
[http://dx.doi.org/10.1038/nchembio.2526] [PMID: 29155429]

Long, D.H.; Townsend, C.A. Mechanism of integrated beta-lactam formation by a nonribosomal peptide synthetase during antibiotic synthesis. Biochemistry, 2018, 57(24), 3353-3358.
[http://dx.doi.org/10.1021/acs.biochem.8b00411] [PMID: 29701951]

Rodríguez-Baño, J.; Gutiérrez-Gutiérrez, B.; Machuca, I.; Pascual, A. Treatment of infections caused by extended-spectrum-beta-lactamase-, AmpC-, and carbapenemase-producing Enterobacteriaceae. Clin. Microbiol. Rev., 2018, 31(2), e00079-e17.
[http://dx.doi.org/10.1128/CMR.00079-17] [PMID: 29444952]

Bush, K.; Page, M.G.P. What we may expect from novel antibacterial agents in the pipeline with respect to resistance and pharmacodynamic principles. J. Pharmacokinet. Pharmacodyn., 2017, 44(2), 113-132.
[http://dx.doi.org/10.1007/s10928-017-9506-4] [PMID: 28161807]

Wright, H.; Bonomo, R.A.; Paterson, D.L. New agents for the treatment of infections with Gram-negative bacteria: Restoring the miracle or false dawn? Clin. Microbiol. Infect., 2017, 23(10), 704-712.
[http://dx.doi.org/10.1016/j.cmi.2017.09.001] [PMID: 28893690]

Jorth, P.; McLean, K.; Ratjen, A.; Secor, P.R.; Bautista, G.E.; Ravishankar, S.; Rezayat, A.; Garudathri, J.; Harrison, J.J.; Harwood, R.A.; Penewit, K.; Waalkes, A.; Singh, P.K.; Salipante, S.J. Evolved aztreonam resistance is multifactorial and can produce hypervirulence in Pseudomonas aeruginosa. MBio, 2017, 8(5), e00517-e17.
[http://dx.doi.org/10.1128/mBio.00517-17] [PMID: 29089424]

Lohans, C.T.; Brem, J.; Schofield, C.J. New Delhi metallo-β-lactamase 1 catalyzes avibactam and aztreonam hydrolysis. Antimicrob. Agents Chemother., 2017, 61(12), e01224-e17.
[http://dx.doi.org/10.1128/AAC.01224-17] [PMID: 28971873]

Sader, H.S.; Mendes, R.E.; Pfaller, M.A.; Shortridge, D.; Flamm, R.K.; Castanheira, M. Antimicrobial activities of aztreonam-avibactam and comparator agents against contemporary (2016) clinical Enterobacteriaceae isolates. Antimicrob. Agents Chemother., 2017, 62(1), e01856-e17.
[http://dx.doi.org/10.1128/AAC.01856-17] [PMID: 29061754]

Wenzler, E.; Deraedt, M.F.; Harrington, A.T.; Danizger, L.H. Synergistic activity of ceftazidime-avibactam and aztreonam against serine and metallo-β-lactamase-producing gram-negative pathogens. Diagn. Microbiol. Infect. Dis., 2017, 88(4), 352-354.
[http://dx.doi.org/10.1016/j.diagmicrobio.2017.05.009] [PMID: 28602518]

Marshall, S.; Hujer, A.M.; Rojas, L.J.; Papp-Wallace, K.M.; Humphries, R.M.; Spellberg, B.; Hujer, K.M.; Marshall, E.K.; Rudin, S.D.; Perez, F.; Wilson, B.M.; Wasserman, R.B.; Chikowski, L.; Paterson, D.L.; Vila, A.J.; van Duin, D.; Kreiswirth, B.N.; Chambers, H.F.; Fowler, V.G., Jr; Jacobs, M.R.; Pulse, M.E.; Weiss, W.J.; Bonomo, R.A. Can ceftazidime-avibactam and aztreonam overcome beta-lactam resistance Conferred by metallo-beta-lactamases in Enterobacteriaceae? Antimicrob. Agents Chemother., 2017, 61(4), e02243-e16.
[http://dx.doi.org/10.1128/AAC.02243-16] [PMID: 28167541]

Mojica, M.F.; Papp-Wallace, K.M.; Taracila, M.A.; Barnes, M.D.; Rutter, J.D.; Jacobs, M.R. LiPuma, J.J.; Walsh, T.J.; Vila, A.J.; Bonomo, R.A. LiPuma, J.J.; Walsh, T.J.; Vila, A.J.; Bonomo, R.A., Avibactam restores the susceptibility of clinical isolates of Stenotrophomonas maltophilia to aztreonam. Antimicrob. Agents Chemother., 2017, 61(10), e00777-e17.
[http://dx.doi.org/10.1128/AAC.00777-17] [PMID: 28784669]

Schalk, I.J.; Mislin, G.L.A. Bacterial iron uptake pathways: Gates for the import of bactericide compounds. J. Med. Chem., 2017, 60(11), 4573-4576.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00554] [PMID: 28453272]

Aztreonam - DrugBank. https://www.drugbank.ca/drugs/DB00355

Górska, A.; Sloderbach, A.; Marszałł, M.P. Siderophore-drug complexes: Potential medicinal applications of the ‘Trojan horse’ strategy. Trends Pharmacol. Sci., 2014, 35(9), 442-449.
[http://dx.doi.org/10.1016/j.tips.2014.06.007] [PMID: 25108321]

Möllmann, U.; Heinisch, L.; Bauernfeind, A.; Köhler, T.; Ankel-Fuchs, D. Siderophores as drug delivery agents: Application of the “Trojan Horse” strategy. Biometals, 2009, 22(4), 615-624.
[http://dx.doi.org/10.1007/s10534-009-9219-2] [PMID: 19214755]

Saha, M.; Sarkar, S.; Sarkar, B.; Sharma, B.K.; Bhattacharjee, S.; Tribedi, P. Microbial siderophores and their potential applications: A review. Environ. Sci. Pollut. Res. Int., 2016, 23(5), 3984-3999.
[http://dx.doi.org/10.1007/s11356-015-4294-0] [PMID: 25758420]

Ji, C.; Juárez-Hernández, R.E.; Miller, M.J. Exploiting bacterial iron acquisition: Siderophore conjugates. Future Med. Chem., 2012, 4(3), 297-313.
[http://dx.doi.org/10.4155/fmc.11.191] [PMID: 22393938]

Foley, T.L.; Simeonov, A. Targeting iron assimilation to develop new antibacterials. Expert Opin. Drug Discov., 2012, 7(9), 831-847.
[http://dx.doi.org/10.1517/17460441.2012.708335] [PMID: 22812521]

Wang, Y.; Fu, H.; Li, Y.; Jiang, J.; Song, D. Synthesis and biological evaluation of 8-substituted berberine derivatives as novel anti-mycobacterial agents. Acta Pharm. Sin. B, 2012, 2(6), 581-587.
[http://dx.doi.org/10.1016/j.apsb.2012.10.008]

Patrick, G.L. An introduction to medicinal chemistry, 5th ed; ; Oxford University Press, United Kingdom: Oxford;, 2017.

Lu, W.; Oberthür, M.; Leimkuhler, C.; Tao, J.; Kahne, D.; Walsh, C.T. Characterization of a regiospecific epivancosaminyl transferase GtfA and enzymatic reconstitution of the antibiotic chloroeremomycin. Proc. Natl. Acad. Sci. USA, 2004, 101(13), 4390-4395.
[http://dx.doi.org/10.1073/pnas.0400277101] [PMID: 15070728]

Bonner, D.P.; Sykes, R.B. Structure activity relationships among the monobactams. J. Antimicrob. Chemother., 1984, 14(4), 313-327.
[http://dx.doi.org/10.1093/jac/14.4.313] [PMID: 6389473]

Walsh, C. Molecular mechanisms that confer antibacterial drug resistance. Nature, 2000, 406(6797), 775-781.
[http://dx.doi.org/10.1038/35021219] [PMID: 10963607]

Rozenfel’d, G.S. Monocyclic beta-lactam antibiotics. Antibiotics Medical Biotech, 1986, 31(4), 302-315.

Luscher, A.; Moynie, L.; Auguste, P.S.; Bumann, D.; Mazza, L.; Pletzer, D.; Naismith, J.H.; Kohler, T. TonB-dependent receptor repertoire of Pseudomonas aeruginosa for uptake of siderophore-drug conjugates. Antimicrob. Agents Chemother., 2018, 62(6), e00097-e18.

Tillotson, G.S. Trojan horse antibiotics-A novel way to circumvent gram-negative bacterial resistance? Infect. Dis. (Auckl.), 2016, 9, 45-52.
[http://dx.doi.org/10.4137/IDRT.S31567] [PMID: 27773991]

Klahn, P.; Brönstrup, M. Bifunctional antimicrobial conjugates and hybrid antimicrobials. Nat. Prod. Rep., 2017, 34(7), 832-885.
[http://dx.doi.org/10.1039/C7NP00006E] [PMID: 28530279]

Ghosh, M.; Miller, P.A.; Möllmann, U.; Claypool, W.D.; Schroeder, V.A.; Wolter, W.R.; Suckow, M.; Yu, H.; Li, S.; Huang, W.; Zajicek, J.; Miller, M.J. Targeted antibiotic delivery: Selective siderophore conjugation with daptomycin confers potent activity against multidrug resistant Acinetobacter baumannii both in-vitro and in-vivo. J. Med. Chem., 2017, 60(11), 4577-4583.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00102] [PMID: 28287735]

Whalan, R.H.; Funnell, S.G.; Bowler, L.D.; Hudson, M.J.; Robinson, A.; Dowson, C.G. Distribution and genetic diversity of the ABC transporter lipoproteins PiuA and PiaA within Streptococcus pneumoniae and related streptococci. J. Bacteriol., 2006, 188(3), 1031-1038.

Ferreira, D.; Seca, A.M.L. C G A, D.; Silva, A.M.S. Targeting human pathogenic bacteria by siderophores: A proteomics review. J. Proteomics, 2016, 145, 153-166.
[http://dx.doi.org/10.1016/j.jprot.2016.04.006] [PMID: 27109355]

Tomaras, A.P.; Crandon, J.L.; McPherson, C.J.; Nicolau, D.P. Potentiation of antibacterial activity of the MB-1 siderophore-monobactam conjugate using an efflux pump inhibitor. Antimicrob. Agents Chemother., 2015, 59(4), 2439-2442.
[http://dx.doi.org/10.1128/AAC.04172-14] [PMID: 25605364]

Fu, H.G.; Hu, X.X.; Li, C.R.; Li, Y.H.; Wang, Y.X.; Jiang, J.D.; Bi, C.W.; Tang, S.; You, X.F.; Song, D.Q. Design, synthesis and biological evaluation of monobactams as antibacterial agents against gram-negative bacteria. Eur. J. Med. Chem., 2016, 110, 151-163.
[http://dx.doi.org/10.1016/j.ejmech.2016.01.024] [PMID: 26827160]

Landman, D.; Singh, M.; El-Imad, B.; Miller, E.; Win, T.; Quale, J. In vitro activity of the siderophore monosulfactam BAL30072 against contemporary Gram-negative pathogens from New York City, including multidrug-resistant isolates. Int. J. Antimicrob. Agents, 2014, 43(6), 527-532.
[http://dx.doi.org/10.1016/j.ijantimicag.2014.02.017] [PMID: 24796217]

van Delden, C.; Page, M.G.; Köhler, T. Involvement of Fe uptake systems and AmpC β-lactamase in susceptibility to the siderophore monosulfactam BAL30072 in Pseudomonas aeruginosa. Antimicrob. Agents Chemother., 2013, 57(5), 2095-2102.
[http://dx.doi.org/10.1128/AAC.02474-12] [PMID: 23422914]

Livermore, D.M.; Woodford, N. The beta-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter. Trends Microbiol., 2006, 14(9), 413-420.
[http://dx.doi.org/10.1016/j.tim.2006.07.008] [PMID: 16876996]

Tfifha, M.; Ferjani, A.; Mallouli, M.; Mlika, N.; Abroug, S.; Boukadida, J. Carriage of multidrug-resistant bacteria among pediatric patients before and during their hospitalization in a tertiary pediatric unit in Tunisia. Libyan J. Med., 2018, 13(1)1419047
[http://dx.doi.org/10.1080/19932820.2017.1419047] [PMID: 29277142]

European Antimicrobial Resistance Surveillance Network (EARS-Net); 2009.Available from: . http//www.earss.rivm.nl

Livermore, D.M. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: Our worst nightmare? Clin. Infect. Dis., 2002, 34(5), 634-640.
[http://dx.doi.org/10.1086/338782] [PMID: 11823954]

Critchley, I.A. Catecholic β-lactams: Facilitated transport. J. Antimicrob. Chemother., 1990, 26(6), 733-735.
[http://dx.doi.org/10.1093/jac/26.6.733] [PMID: 2081714]

Page, M.G.; Dantier, C.; Desarbre, E. In vitro properties of BAL30072, a novel siderophore sulfactam with activity against multiresistant gram-negative bacilli. Antimicrob. Agents Chemother., 2010, 54(6), 2291-2302.
[http://dx.doi.org/10.1128/AAC.01525-09] [PMID: 20308379]

Flanagan, M.E.; Brickner, S.J.; Lall, M.; Casavant, J.; Deschenes, L.; Finegan, S.M.; George, D.M.; Granskog, K.; Hardink, J.R.; Huband, M.D.; Hoang, T.; Lamb, L.; Marra, A.; Mitton-Fry, M.; Mueller, J.P.; Mullins, L.M.; Noe, M.C.; O’Donnell, J.P.; Pattavina, D.; Penzien, J.B.; Schuff, B.P.; Sun, J.; Whipple, D.A.; Young, J.; Gootz, T.D. Preparation, gram-negative antibacterial activity, and hydrolytic stability of novel siderophore-conjugated monocarbam diols. ACS Med. Chem. Lett., 2011, 2(5), 385-390.
[http://dx.doi.org/10.1021/ml200012f] [PMID: 24900319]

Schuff, B.; Mitton-Fry, M.; Arcari, J.; Brown, M.; Casavant, J.; Flanagan, M.; Gerstenberger, B.; Harris, T.; Hoang, T.; Lall, M. Abstracts of Papers. 245^th ACS National Meeting & Exposition, New Orleans, LA, United States2013.

Richardson, D.R.; Hefter, G.T.; May, P.M.; Webb, J.; Baker, E. Iron chelators of the pyridoxal isonicotinoyl hydrazone class. III. Formation constants with calcium(II), magnesium(II) and zinc(II). Biol. Met., 1989, 2(3), 161-167.
[http://dx.doi.org/10.1007/BF01142555] [PMID: 2490071]

Kline, T.; Fromhold, M.; McKennon, T.E.; Cai, S.; Treiberg, J.; Ihle, N.; Sherman, D.; Schwan, W.; Hickey, M.J.; Warrener, P.; Witte, P.R.; Brody, L.L.; Goltry, L.; Barker, L.M.; Anderson, S.U.; Tanaka, S.K.; Shawar, R.M.; Nguyen, L.Y.; Langhorne, M.; Bigelow, A.; Embuscado, L.; Naeemi, E. Antimicrobial effects of novel siderophores linked to beta-lactam antibiotics. Bioorg. Med. Chem., 2000, 8(1), 73-93.
[http://dx.doi.org/10.1016/S0968-0896(99)00261-8] [PMID: 10968267]

Link, G.; Ponka, P.; Konijn, A.M.; Breuer, W.; Cabantchik, Z.I.; Hershko, C. Effects of combined chelation treatment with pyridoxal isonicotinoyl hydrazone analogs and deferoxamine in hypertransfused rats and in iron-loaded rat heart cells. Blood, 2003, 101(10), 4172-4179.
[http://dx.doi.org/10.1182/blood-2002-08-2382] [PMID: 12511418]

Miethke, M.; Marahiel, M.A. Siderophore-based iron acquisition and pathogen control. Microbiol. Mol. Biol. Rev., 2007, 71(3), 413-451.
[http://dx.doi.org/10.1128/MMBR.00012-07] [PMID: 17804665]

Skaar, E.P. The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS Pathog., 2010, 6(8)e1000949
[http://dx.doi.org/10.1371/journal.ppat.1000949] [PMID: 20711357]

Hannauer, M.; Yeterian, E.; Martin, L.W.; Lamont, I.L.; Schalk, I.J. An efflux pump is involved in secretion of newly synthesized siderophore by Pseudomonas aeruginosa. FEBS Lett., 2010, 584(23), 4751-4755.
[http://dx.doi.org/10.1016/j.febslet.2010.10.051] [PMID: 21035449]

Cornelis, P. Iron uptake and metabolism in pseudomonads. Appl. Microbiol. Biotechnol., 2010, 86(6), 1637-1645.
[http://dx.doi.org/10.1007/s00253-010-2550-2] [PMID: 20352420]

Hider, R.C.; Kong, X. Chemistry and biology of siderophores. Nat. Prod. Rep., 2010, 27(5), 637-657.
[http://dx.doi.org/10.1039/b906679a] [PMID: 20376388]

Budzikiewicz, H. Siderophore-antibiotic conjugates used as trojan horses against Pseudomonas aeruginosa. Curr. Top. Med. Chem., 2001, 1(1), 73-82.
[http://dx.doi.org/10.2174/1568026013395524] [PMID: 11895295]

Page, M.G.; Heim, J. Prospects for the next anti-pseudomonas drug. Curr. Opin. Pharmacol., 2009, 9(5), 558-565.
[http://dx.doi.org/10.1016/j.coph.2009.08.006] [PMID: 19748829]

Möllmann, U.; Heinisch, L.; Bauernfeind, A.; Köhler, T.; Ankel-Fuchs, D. Siderophores as drug delivery agents: Application of the “Trojan Horse” strategy. Biometals, 2009, 22(4), 615-624.
[http://dx.doi.org/10.1007/s10534-009-9219-2] [PMID: 19214755]

Carosso, S.; Liu, R.; Miller, P.A.; Hecker, S.J.; Glinka, T.; Miller, M.J. Methodology for monobactam diversification: Syntheses and studies of 4-thiomethyl substituted beta-lactams with activity against gram-negative bacteria, including carbapenemase producing acinetobacter baumannii. J. Med. Chem., 2017, 60(21), 8933-8944.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01164] [PMID: 28994597]

Yoshida, C.; Tanaka, K.; Todo, Y.; Hattori, R.; Fukuoka, Y.; Komatsu, M.; Saikawa, I. Studies on monocyclic beta-lactam antibiotics. IV. Synthesis and antibacterial activity of (3S,4R)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-(O-substituted oxyimino)acetamido]-4-methyl-1- (1H-tetrazol-5-yl)-2-azetidinones. J. Antibiot. (Tokyo), 1986, 39(1), 90-100.
[http://dx.doi.org/10.7164/antibiotics.39.90] [PMID: 3081473]

Han, S.; Zaniewski, R.P.; Marr, E.S.; Lacey, B.M.; Tomaras, A.P.; Evdokimov, A.; Miller, J.R.; Shanmugasundaram, V. Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA, 2010, 107(51), 22002-22007.
[http://dx.doi.org/10.1073/pnas.1013092107] [PMID: 21135211]

Majewski, M.W.; Watson, K.D.; Cho, S.; Miller, P.A.; Franzblau, S.G.; Miller, M.J. Syntheses and biological evaluations of highly functionalized hydroxamate containing and N-methylthio monobactams as anti-tuberculosis and beta-lactamase inhibitory agents. MedChemComm, 2016, 7(1), 141-147.
[http://dx.doi.org/10.1039/C5MD00340G] [PMID: 26918106]

a)Page, M.I. The reactivity of beta-lactams, the mechanism of catalysis and the inhibition of beta-lactamases. Curr. Pharm. Des., 1999, 5(11), 895-913.
[PMID: 10539995]
b)Cherian, P.T.; Deshpande, A.; Cheramie, M.N.; Bruhn, D.F.; Hurdle, J.G.; Lee, R.E. Design, synthesis and microbiological evaluation of ampicillin-tetramic acid hybrid antibiotics. J. Antibiot. (Tokyo), 2017, 70(1), 65-72.
[http://dx.doi.org/10.1038/ja.2016.52] [PMID: 27189120]

Chen, D.; Falsetti, S.C.; Frezza, M.; Milacic, V.; Kazi, A.; Cui, Q.C.; Long, T.E.; Turos, E.; Dou, Q.P. Anti-tumor activity of N-thiolated β-lactam antibiotics. Cancer Lett., 2008, 268(1), 63-69.
[http://dx.doi.org/10.1016/j.canlet.2008.03.047] [PMID: 18468785]

Turos, E.; Shim, J.Y.; Wang, Y.; Greenhalgh, K.; Reddy, G.S.K.; Dickey, S.; Lim, D.V. Antibiotic-conjugated polyacrylate nanoparticles: New opportunities for development of anti-MRSA agents. Bioorg. Med. Chem. Lett., 2007, 17(1), 53-56.
[http://dx.doi.org/10.1016/j.bmcl.2006.09.098] [PMID: 17049850]

Fischbach, M.A.; Walsh, C.T. Antibiotics for emerging pathogens. Science, 2009, 325(5944), 1089-1093.
[http://dx.doi.org/10.1126/science.1176667] [PMID: 19713519]

Gaunt, M.J.; Johansson, C.C.; McNally, A.; Vo, N.T. Enantioselective organocatalysis. Drug Discov. Today, 2007, 12(1-2), 8-27.
[http://dx.doi.org/10.1016/j.drudis.2006.11.004] [PMID: 17198969]

MacMillan, D.W. The advent and development of organocatalysis. Nature, 2008, 455(7211), 304-308.
[http://dx.doi.org/10.1038/nature07367] [PMID: 18800128]

Pawar, S.A.; Alapour, S.; Khanyase, S.; Cele, Z.E.; Chitti, S.; Kruger, H.G.; Govender, T.; Arvidsson, P.I. Organocatalyzed stereospecific C-C bond formation of β-lactams. Org. Biomol. Chem., 2013, 11(48), 8294-8297.
[http://dx.doi.org/10.1039/C3OB41858H] [PMID: 24217690]

Avenoza, A.; Barriobero, J.I.; Busto, J.H.; Peregrina, J.M. Enantiopure synthesis of all four stereoisomers of carbapenam-3-carboxylic acid methyl ester. J. Org. Chem., 2003, 68(7), 2889-2894.
[http://dx.doi.org/10.1021/jo026804+] [PMID: 12662066]

Salunkhe, D.S.; Piste, P.B. A brief review on recent synthesis of 2-azetidinone derivatives. Int. J. Pharm. Sci. Res., 2014, 5, 666-689.

a)Vazhappilly, C.G.; Saleh, E.; Ramadan, W.; Menon, V.; Al-Azawi, A.M.; Tarazi, H.; Abdu-Allah, H.; El-Shorbagi, A.N.; El-Awady, R. Inhibition of SHP2 by new compounds induces differential effects on RAS/RAF/ERK and PI3K/AKT pathways in different cancer cell types. Invest. New Drugs, 2018, 1-10.
b)El-Shorbagi, A.N.; El-Naggar, M.; Tarazi, H.; Chaudhary, S.; Abdu-Allah, H.; Hersi, F.; Omar, H. Bis-(5-substituted-2-thiono-1,3,5-thiadiazinan-3-yl) butane as a scaffold of anti-proliferative activity, blended by a multicomponent process. Med. Chem. Res., 2018, 27(4), 1103-1110.
c)Abdu-Allah, H.H.; Abdel-Moty, S.G.; El-Awady, R.; El-Shorbagi, A.N. Design and synthesis of novel 5-aminosalicylate (5-ASA)-4-thiazolinone hybrid derivatives with promising antiproliferative activity. Bioorg. Med. Chem. Lett., 2016, 26(7), 1647-1650.
d)El-Shorbagi, A.A.; Abdel-Moty, S.G.; Ahmed, A.N.; Takayama, H.; Kitajima, M.; Aimi, N.; Sakai, S. The antiviral (RNA & DNA) profile of some incomplete C-nucleosides inspired from natural ß-carboline (pyrido [3,4-b] indole) scaffold; pharmacology of the intermediates in the total synthesis. Pharma Chem., 2015, 11, 87-92.
e)El-Shorbagi, A-N.A.; Husein, M.A. Synthesis and investigation of antihypertensive activity using anaesthetizednormotensive nonhuman primates of some 2-aryl-4-(substituted) pyrimido-[1,2-a] benzimidazoles. Pharma Chem., 2015, 7(4), 190-200.
f)El-Shorbagi, A-N.A.; Husein, M.A. An approach to hypertension crisis: Evaluation of new fused banzazoles; 2-arylethenyl and 2,4-bis(arylethenyl) derivatives derived from 2,4-dimethylpyrimido [1,2-a] benzimidazole. Pharma Chem., 2015, 7(5), 319-328.
g)Amin, E.N.; Abdel-Alim, A.A.; Abdel-Moty, S.G.; El-Shorbagi, A.N.; Abdel-Rahman, M.Sh. Synthesis of new 4,5-3(2H)pyridazinone derivatives and their cardiotonic, hypotensive, and platelet aggregation inhibition activities. Arch. Pharm. Res., 2010, 33(1), 25-46.
h)El Bialy, S.A.; Abdelal, A.M.; El-Shorbagi, A.N.; Kheira, S.M. 2, 3-Bis(5-alkyl-2-thiono-1, 3, 5-thiadiazin-3-yl) propionic acid: one-pot domino synthesis and antimicrobial activity. Arch. Pharm. (Weinheim), 2005, 338(1), 38-43.
i)Abdel-Moty, S.G.; Sakai, S.; Aimi, N.; Takayama, H.; Kitajima, M.; El-Shorbagi, A.; Ahmed, A.N.; Omar, N.M. Synthesis of cytotoxic 1-polyhydroxyalkyl-β-carboline derivatives. Eur. J. Med. Chem., 1998, 32(12), 1009-1017.
j)Abd-Elrahman, M.I.; Ahmed, M.O.; Ahmed, S.M. aboul-Fadl, T.; El-Shorbagi, A. Kinetics of solid state stability of glycine derivatives as a model for peptides using differential scanning calorimetry. Biophys. Chem., 2002, 97(2-3), 113-120.
k)Abdu-Allah, H.; Abdelmoez, A.; Tarazi, H.; El-Shorbagi, A-N.; El-Awady, R. Conjugation of 4-aminosalicylate with thiazolinones afforded non-cytotoxic potent in vitro and in vivo anti-inflammatory hybrids. Bioorg. Chem., 2019, 103378
[http://dx.doi.org/10.1016/j.bioorg.2019.103378]
l)Aboul-Fadl, T.; El Shorbagi, A.N. New carriers for representative peptides and peptide drugs. Arch. Pharm. (Weinheim), 1997, 330(11), 327-332.
m)Aboul-Fadl, T.; El-Shorbagi, A.N.; Hozien, Z.A.; Sarhan, A.W. Investigation of alkylating, antineoplastic and anti-HIV potentials of the chalcones: 2-(3-arylpropenoyl)benzimidazole and their corresponding N1-methyl derivatives. Boll. Chim. Farm., 2000, 139(5), 228-234.
n)Aboul-Fadl, T.; Hussein, M.A.; El-Shorbagi, A.N.; Khallil, A.R. New 2H-tetrahydro-1, 3, 5-thiadiazine-2-thiones incorporating glycine and glycinamide as potential antifungal agents. Arch. Pharm. (Weinheim), 2002, 335(9), 438-442.
o)El-Shorbagi, A.N. New tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives as potential antimicrobial agents. Arch. Pharm. (Weinheim), 2000, 333(9), 281-286.
p)Mohamed, M.H.; El-Shorbagi, A-N.A. (±)-termisine, a novel lupine alkaloid from the seeds of Lupinus termis. J. Nat. Prod., 1993, 56(11), 1999-2002.
q)El-Shorbagi, A-N.A.; Sakai, S-I.; El-Gendy, M.A.; Omar, N.; Farag, H.H. Imidazo [2,1-b] benzothiazoles. I. Chem. Pharm. Bull. (Tokyo), 1988, 36(12), 4760-4768.
r)Emara, S.; El-Gindy, A.; El-Shorbagi, A-N.A.; Hadad, G. Utility of copper (II) oxide as a packed reactor in flow injection assembly for rapid analysis of some angiotensin converting enzyme inhibitors. Anal. Chim. Acta, 2003, 489(1), 115-123.
s)Emara, S.; Razee, S.; El-Shorbagi, A-N.; Masujima, T. Flow injection method for the determination of methotrexate with a column-packed oxidizing agent. Analyst (Lond.), 1996, 121(2), 183-188.
t)Abdel-Alim, A.A.; El-Shorbagi, A.N.; Abdel-Moty, S.G.; Abdel-Allah, H.H. Synthesis and anti-inflammatory testing of some new compounds incorporating 5-aminosalicylic acid (5-ASA) as potential prodrugs. Arch. Pharm. Res., 2005, 28(6), 637-647.
[http://dx.doi.org/10.1007/BF02969351] [PMID: 16042070]

a)Hussein, A.H.; El-Shorbagi, A.A.; Omar, N.M.; Farghaly, Z.S.; Tomioka, K. New chiral amine ligands for enantioselective synthesis of certain (S)-and (R)-monobactams. Bull. Pharm. Sci., 2000, 23(2), 125-136.
bHussein, M.A.; Iida, A.; Tomioka, K. Studies aimed at enhancement of reactivity and enantioselectivity of a lithium ester enolate using a chiral tridentate lithium amide. Tetrahedron, 1999, 55(37), 11219-11228.
[http://dx.doi.org/10.1016/S0040-4020(99)00644-4]

Kojo, H.; Mine, Y.; Nishida, M.; Goto, S.; Kuwahara, S. Nature of monocyclic beta-lactam antibiotic Nocardicin A to beta-lactamases. Microbiol. Immunol., 1988, 32(2), 119-130.
[http://dx.doi.org/10.1111/j.1348-0421.1988.tb01371.x] [PMID: 3287105]

Davidsen, J.M.; Townsend, C.A. In vivo characterization of nonribosomal peptide synthetases NocA and NocB in the biosynthesis of nocardicin A. Chem. Biol., 2012, 19(2), 297-306.
[http://dx.doi.org/10.1016/j.chembiol.2011.10.020] [PMID: 22365611]

Mine, Y.; Nonoyama, S.; Kojo, H.; Fukada, S.; Nishida, M.; Nocardicin, A. Nocardicin A, a new monocyclic beta-lactam antibiotic V. In vivo evaluation. J. Antibiot. (Tokyo), 1977, 30(11), 932-937.
[http://dx.doi.org/10.7164/antibiotics.30.932] [PMID: 338567]

Horsman, M.E.; Marous, D.R.; Li, R.; Oliver, R.A.; Byun, B.; Emrich, S.J.; Boggess, B.; Townsend, C.A.; Mobashery, S. Whole-genome shotgun sequencing of Two beta-proteobacterial species in search of the bulgecin biosynthetic cluster. ACS Chem. Biol., 2017, 12(10), 2552-2557.
[http://dx.doi.org/10.1021/acschembio.7b00687] [PMID: 28937735]

Braga, D.; Lackner, G. One Ring to fight them all: The sulfazecin story. Cell Chem. Biol., 2017, 24(1), 1-2.
[http://dx.doi.org/10.1016/j.chembiol.2017.01.001] [PMID: 28107651]

Imada, A.; Kitano, K.; Kintaka, K.; Muroi, M.; Asai, M. Sulfazecin and isosulfazecin, novel beta-lactam antibiotics of bacterial origin. Nature, 1981, 289(5798), 590-591.
[http://dx.doi.org/10.1038/289590a0] [PMID: 7007891]

Parker, W.L.; O’Sullivan, J.; Sykes, R.B. Naturally occurring monobactams. Adv. Appl. Microbiol., 1986, 31, 181-205.
[http://dx.doi.org/10.1016/S0065-2164(08)70442-8] [PMID: 3521210]

Nishida, M.; Mine, Y.; Nonoyama, S.; Kojo, H.; Nocardicin, A. Nocardicin A, a new monocyclic beta-lactam antibiotic III. In vitro evaluation. J. Antibiot. (Tokyo), 1977, 30(11), 917-925.
[http://dx.doi.org/10.7164/antibiotics.30.917] [PMID: 412823]

Kojo, H.; Mine, Y.; Nishida, M.; Nocardicin, A. Nocardicin A, a new monocyclic beta-lactam antibiotic IV. Factors influencing the in vitro activity of Nocardicin A. J. Antibiot. (Tokyo), 1977, 30(11), 926-931.
[http://dx.doi.org/10.7164/antibiotics.30.926] [PMID: 412824]

Nisbet, L.J.; Mehta, R.J.; Oh, Y.; Pan, C.H.; Phelen, C.G.; Polansky, M.J.; Shearer, M.C.; Giovenella, A.J.; Grappel, S.F. Chlorocardicin, a monocyclic beta-lactam from a Streptomyces sp. I. Discovery, production and biological activities. J. Antibiot. (Tokyo), 1985, 38(2), 133-138.
[http://dx.doi.org/10.7164/antibiotics.38.133] [PMID: 3922933]

Li, R.; Oliver, R.A.; Townsend, C.A. Identification and characterization of the sulfazecin monobactam biosynthetic gene cluster. Cell Chem. Biol., 2017, 24(1), 24-34.
[http://dx.doi.org/10.1016/j.chembiol.2016.11.010] [PMID: 28017601]

Gaudelli, N.M.; Long, D.H.; Townsend, C.A. β-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis. Nature, 2015, 520(7547), 383-387.
[http://dx.doi.org/10.1038/nature14100] [PMID: 25624104]

O’Sullivan, J.; Abraham, E.P. The conversion of cephalosporins to 7 alpha-methoxycephalosporins by cell-free extracts of Streptomyces clavuligerus. Biochem. J., 1980, 186(2), 613-616.
[http://dx.doi.org/10.1042/bj1860613] [PMID: 7378068]

Box, S.J.; Brown, A.G.; Gilpin, M.L.; Gwynn, M.N.; Spear, S.R. MM 42842, a new member of the monobactam family produced by Pseudomonas cocovenenans. II. Production, isolation and properties of MM 42842. J. Antibiot. (Tokyo), 1988, 41(1), 7-12.
[http://dx.doi.org/10.7164/antibiotics.41.7] [PMID: 3346195]

Sykes, R.B.; Bonner, D.P.; Bush, K.; Georgopapadakou, N.H. Azthreonam (SQ 26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria. Antimicrob. Agents Chemother., 1982, 21(1), 85-92.
[http://dx.doi.org/10.1128/AAC.21.1.85] [PMID: 6979307]

Kishimoto, S.; Sendai, M.; Hashiguchi, S.; Tomimoto, M.; Satoh, Y.; Matsuo, T.; Kondo, M.; Ochiai, M. Synthesis of sulfazecin-type 2-azetidinones with a carbon substituent at the 4-position. J. Antibiot. (Tokyo), 1983, 36(10), 1421-1424.
[http://dx.doi.org/10.7164/antibiotics.36.1421] [PMID: 6358173]

Yoshida, K.; Mitani, M.; Naeshiro, I.; Torii, H.; Tanayama, S. Disposition of carumonam (AMA-1080/Ro 17-2301), a new N-sulfonated monocyclic beta-lactam, in rats and dogs. Antimicrob. Agents Chemother., 1986, 29(6), 1017-1024.
[http://dx.doi.org/10.1128/AAC.29.6.1017] [PMID: 3729358]

Imada, A.; Kondo, M.; Okonogi, K.; Yukishige, K.; Kuno, M. In vitro and in vivo antibacterial activities of carumonam (AMA-1080), a new N-sulfonated monocyclic beta-lactam antibiotic. Antimicrob. Agents Chemother., 1985, 27(5), 821-827.
[http://dx.doi.org/10.1128/AAC.27.5.821] [PMID: 3874598]

Kita, Y.; Fugono, T.; Imada, A. Comparative pharmacokinetics of carumonam and aztreonam in mice, rats, rabbits, dogs, and cynomolgus monkeys. Antimicrob. Agents Chemother., 1986, 29(1), 127-134.
[http://dx.doi.org/10.1128/AAC.29.1.127] [PMID: 3729325]

Ng, W.W.; Chau, P.Y.; Leung, Y.K.; Livermore, D.M. In vitro activities of Ro 17-2301 and aztreonam compared with those of other new beta-lactam antibiotics against clinical isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother., 1985, 27(5), 872-873.
[http://dx.doi.org/10.1128/AAC.27.5.872] [PMID: 3925877]

McCullough, B.J.; Wiggins, L.E.; Richards, A.; Klinker, K.; Hiemenz, J.W.; Wingard, J.R. Aztreonam for febrile neutropenia in patients with beta-lactam allergy. Transpl. Infect. Dis., 2014, 16(1), 145-152.
[http://dx.doi.org/10.1111/tid.12148] [PMID: 24119095]

de Vries-Hospers, H.G.; Welling, G.W.; Swabb, E.A.; van der Waaij, D. Selective decontamination of the digestive tract with aztreonam: A study of 10 healthy volunteers. J. Infect. Dis., 1984, 150(5), 636-642.
[http://dx.doi.org/10.1093/infdis/150.5.636] [PMID: 6541674]

McNulty, C.A.; Garden, G.M.; Ashby, J.; Wise, R. Pharmacokinetics and tissue penetration of carumonam, a new synthetic monobactam. Antimicrob. Agents Chemother., 1985, 28(3), 425-427.
[http://dx.doi.org/10.1128/AAC.28.3.425] [PMID: 4073864]

Wise, R.; Gillett, A.P.; Cadge, B.; Durham, S.R.; Baker, S. The influence of protein binding upon tissue fluid levels of six beta-lactam antibiotics. J. Infect. Dis., 1980, 142(1), 77-82.
[http://dx.doi.org/10.1093/infdis/142.1.77] [PMID: 7400630]

Fracasso, M.E.; Consolo, V.; Ferronato, G.; Leone, R.; Cuzzolin, L.; Benoni, G. Aztreonam penetration of bone and soft tissue, after I.V. infusion and bolus injection. J. Antimicrob. Chemother., 1989, 23(3), 465-467.
[http://dx.doi.org/10.1093/jac/23.3.465] [PMID: 2732130]

Takabayashi, H.; Kuwabara, S. Tissue penetration of aztreonam in obstetrics and gynecology. Jpn. J. Antibiot., 1985, 38(12), 3606-3608.
[PMID: 3834145]

Whitby, M.; Hempenstall, J.; Gilpin, C.; Weir, L.; Nimmo, G. Penetration of monobactam antibiotics (aztreonam, carumonam) into human prostatic tissue. Chemotherapy, 1989, 35(1), 7-11.
[http://dx.doi.org/10.1159/000238629] [PMID: 2721291]

Weidekamm, E.; Stoeckel, K.; Egger, H.J.; Ziegler, W.H. Single-dose pharmacokinetics of Ro 17-2301 (AMA-1080), a monocyclic beta-lactam, in humans. Antimicrob. Agents Chemother., 1984, 26(6), 898-902.
[http://dx.doi.org/10.1128/AAC.26.6.898] [PMID: 6395801]

1-[(1s)-Carboxy-2-(Methylsulfinyl)Ethyl]-(3r)-[(5s)-5-Amino-5- Carboxypentanamido]-(4r)-Sulfanylazetidin-2-One. Available from . https://www.drugbank.ca/drugs/DB03004

Fuchs, P.C.; Jones, R.N.; Barry, A.L. In vitro antimicrobial activity of tigemonam, a new orally administered monobactam. Antimicrob. Agents Chemother., 1988, 32(3), 346-349.
[http://dx.doi.org/10.1128/AAC.32.3.346] [PMID: 3259122]

Chin, N.X.; Neu, H.C. Tigemonam, an oral monobactam. Antimicrob. Agents Chemother., 1988, 32(1), 84-91.
[http://dx.doi.org/10.1128/AAC.32.1.84] [PMID: 3279906]

Bodey, G.; Reuben, A.; Elting, L.; Kantarjian, H.; Keating, M.; Hagemeister, F.; Koller, C.; Velasquez, W.; Papadopoulos, N. Comparison of two schedules of cefoperazone plus aztreonam in the treatment of neutropenic patients with fever. Eur. J. Clin. Microbiol. Infect. Dis., 1991, 10(7), 551-558.
[http://dx.doi.org/10.1007/BF01967272] [PMID: 1915397]

Fishman, A.; Chowers, M.; Altaras, M.; Beyth, Y.; Lang, R. Aztreonam plus piperacillin-empiric treatment of neutropenic fever in gynecology-oncology patients receiving cisplatin-based chemotherapy. Eur. J. Gynaecol. Oncol., 1998, 19(2), 126-129.
[PMID: 9611050]

a)Sendai, M.; Hashiguchi, S.; Tomimoto, M.; Kishimoto, S.; Matsuo, T.; Kondo, M.; Ochiai, M. Chemical modification of sulfazecin. Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives. J. Antibiot. (Tokyo), 1985, 38(3), 346-371.
[http://dx.doi.org/10.7164/antibiotics.38.346] [PMID: 4008329]
b)Matsuda, K.; Nakagawa, S.; Nakano, F.; Inoue, M.; Mitsuhashi, S. Structure-activity relations of 4-fluoromethyl monobactams. J. Antimicrob. Chemother., 1987, 19(6), 753-760.
[http://dx.doi.org/10.1093/jac/19.6.753] [PMID: 3497148]

Poirel, L.; Naas, T.; Guibert, M.; Chaibi, E.B.; Labia, R.; Nordmann, P. Molecular and biochemical characterization of VEB-1, a novel class A extended-spectrum beta-lactamase encoded by an Escherichia coli integron gene. Antimicrob. Agents Chemother., 1999, 43(3), 573-581.
[http://dx.doi.org/10.1128/AAC.43.3.573] [PMID: 10049269]

Paterson, D.L.; Bonomo, R.A. Extended-spectrum beta-lactamases: A clinical update. Clin. Microbiol. Rev., 2005, 18(4), 657-686.
[http://dx.doi.org/10.1128/CMR.18.4.657-686.2005] [PMID: 16223952]

Logan, L.K.; Hujer, A.M.; Marshall, S.H.; Domitrovic, T.N.; Rudin, S.D.; Zheng, X.; Qureshi, N.K.; Hayden, M.K.; Scaggs, F.A.; Karadkhele, A.; Bonomo, R.A. Analysis of β-lactamase resistance determinants in Enterobacteriaceae from chicago children: A Multicenter Survey. Antimicrob. Agents Chemother., 2016, 60(6), 3462-3469.
[http://dx.doi.org/10.1128/AAC.00098-16] [PMID: 27021322]

McPherson, C.J.; Aschenbrenner, L.M.; Lacey, B.M.; Fahnoe, K.C.; Lemmon, M.M.; Finegan, S.M.; Tadakamalla, B.; O’Donnell, J.P.; Mueller, J.P.; Tomaras, A.P. Clinically relevant Gram-negative resistance mechanisms have no effect on the efficacy of MC-1, a novel siderophore-conjugated monocarbam. Antimicrob. Agents Chemother., 2012, 56(12), 6334-6342.
[http://dx.doi.org/10.1128/AAC.01345-12] [PMID: 23027195]

(a) Bains, G.; Freire, E. Calorimetric determination of cooperative interactions in high affinity binding processes. Anal. Biochem., 1991, 192(1), 203-206.
[http://dx.doi.org/10.1016/0003-2697(91)90207-A] [PMID: 2048721]
(b) Dean, C.R.; Barkan, D.T.; Bermingham, A.; Blais, J.; Casey, F.; Casarez, A.; Colvin, R.; Fuller, J.; Jones, A.K.; Li, C.; Lopez, S.; Metzger, L.E., IV; Mostafavi, M.; Prathapam, R.; Rasper, D.; Reck, F.; Ruzin, A.; Shaul, J.; Shen, X.; Simmons, R.L.; Skewes-Cox, P.; Takeoka, K.T.; Tamrakar, P.; Uehara, T.; Wei, J.R. Mode of action of the monobactam LYS228 and mechanisms decreasing in vitro susceptibility in Escherichia coli and Klebsiella pneumoniae. Antimicrob. Agents Chemother., 2018, 62(10), e0200-e0218.
[http://dx.doi.org/10.1128/AAC.01200-18] [PMID: 30061293]
(c) Reck, F.; Bermingham, A.; Blais, J.; Capka, V.; Cariaga, T.; Casarez, A.; Colvin, R.; Dean, C.R.; Fekete, A.; Gong, W.; Growcott, E.; Guo, H.; Jones, A.K.; Li, C.; Li, F.; Lin, X.; Lindvall, M.; Lopez, S.; McKenney, D.; Metzger, L.; Moser, H.E.; Prathapam, R.; Rasper, D.; Rudewicz, P.; Sethuraman, V.; Shen, X.; Shaul, J.; Simmons, R.L.; Tashiro, K.; Tang, D.; Tjandra, M.; Turner, N.; Uehara, T.; Vitt, C.; Whitebread, S.; Yifru, A.; Zang, X.; Zhu, Q. Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae - Identification of LYS228. Bioorg. Med. Chem. Lett., 2018, 28(4), 748-755.
[http://dx.doi.org/10.1016/j.bmcl.2018.01.006] [PMID: 29336873]
(d) Jones, A.K.; Ranjitkar, S.; Lopez, S.; Li, C.; Blais, J.; Reck, F.; Dean, C.R. Impact of Inducible blaDHA-1 on susceptibility of Klebsiella pneumoniae clinical isolates to LYS228 and identification of chromosomal mpl and ampD mutations mediating upregulation of plasmid-borne blaDHA-1 expression. Antimicrob. Agents Chemother., 2018, 62(10), e01202-e01218.
[http://dx.doi.org/10.1128/AAC.01202-18] [PMID: 30061296]
(e) Blais, J.; Lopez, S.; Li, C.; Ruzin, A.; Ranjitkar, S.; Dean, C.R.; Leeds, J.A.; Casarez, A.; Simmons, R.L.; Reck, F. In vitro activity of LYS228, a novel monobactam antibiotic, against multidrug-resistant enterobacteriaceae. Antimicrob. Agents Chemother., 2018, 62(10), e00552-e18.
[http://dx.doi.org/10.1128/AAC.00552-18] [PMID: 30038040]

Romano, A.; Gaeta, F.; Valluzzi, R.L.; Caruso, C.; Rumi, G.; Bousquet, P.J. IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. J. Allergy Clin. Immunol., 2010, 126(5), 994-999.
[http://dx.doi.org/10.1016/j.jaci.2010.06.052] [PMID: 20888035]

Tateda, K.; Ishii, Y.; Matsumoto, T.; Yamaguchi, K. ‘Break-point Checkerboard Plate’ for screening of appropriate antibiotic combinations against multidrug-resistant Pseudomonas aeruginosa. Scand. J. Infect. Dis., 2006, 38(4), 268-272.
[http://dx.doi.org/10.1080/00365540500440353] [PMID: 16709527]

Araoka, H.; Baba, M.; Takagi, S.; Matsuno, N.; Ishiwata, K.; Nakano, N.; Tsuji, M.; Yamamoto, H.; Seo, S.; Asano-Mori, Y.; Uchida, N.; Masuoka, K.; Wake, A.; Taniguchi, S.; Yoneyama, A. Monobactam and aminoglycoside combination therapy against metallo-beta-lactamase-producing multidrug-resistant Pseudomonas aeruginosa screened using a ‘break-point checkerboard plate’. Scand. J. Infect. Dis., 2010, 42(3), 231-233.
[http://dx.doi.org/10.3109/00365540903443157] [PMID: 20001223]

Chan, W.; Taylor, A.J.; Ellims, A.H.; Lefkovits, L.; Wong, C.; Kingwell, B.A.; Natoli, A.; Croft, K.D.; Mori, T.; Kaye, D.M.; Dart, A.M.; Duffy, S.J. Effect of iron chelation on myocardial infarct size and oxidative stress in ST-elevation-myocardial infarction. Circ. Cardiovasc. Interv., 2012, 5(2), 270-278.
[http://dx.doi.org/10.1161/CIRCINTERVENTIONS.111.966226] [PMID: 22496085]

Voskaridou, E.; Komninaka, V.; Karavas, A.; Terpos, E.; Akianidis, V.; Christoulas, D. Combination therapy of deferasirox and deferoxamine shows significant improvements in markers of iron overload in a patient with β-thalassemia major and severe iron burden. Transfusion, 2014, 54(3), 646-649.
[http://dx.doi.org/10.1111/trf.12335] [PMID: 23834310]

Uygun, V.; Kurtoglu, E. Iron-chelation therapy with oral chelators in patients with thalassemia major. Hematology, 2013, 18(1), 50-55.
[http://dx.doi.org/10.1179/1607845412Y.0000000046] [PMID: 23321010]

Choi, J.J.; McCarthy, M.W. Cefiderocol: A novel siderophore cephalosporin. Expert Opin. Investig. Drugs, 2018, 27(2), 193-197.
[http://dx.doi.org/10.1080/13543784.2018.1426745] [PMID: 29318906]

Wager, T.T.; Hou, X.; Verhoest, P.R.; Villalobos, A. Central nervous system multiparameter optimization desirability: Application in drug discovery. ACS Chem. Neurosci., 2016, 7(6), 767-775.
[http://dx.doi.org/10.1021/acschemneuro.6b00029] [PMID: 26991242]

Tsaioun, K.; Blaauboer, B.J.; Hartung, T. Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods. ALTEX, 2016, 33(4), 343-358.
[http://dx.doi.org/10.14573/altex.1610101] [PMID: 27806179]

Tremaine, L.; Brian, W.; DelMonte, T.; Francke, S.; Groenen, P.; Johnson, K.; Li, L.; Pearson, K.; Marshall, J.C. The role of ADME pharmacogenomics in early clinical trials: Perspective of the industry pharmacogenomics working group (I-PWG). Pharmacogenomics, 2015, 16(18), 2055-2067.
[http://dx.doi.org/10.2217/pgs.15.141] [PMID: 26616152]