2.1 Introduction
45
2016 (Vjecha et al. 2018). In theory, extensions to include one or more dual or triple
action hybrids (and/or associated prodrugs) in the five component mixture would
extend the activity profile beyond five separate single actions, but it is considered
less likely to be realised in practice though.
2.2 Summary
The investigation of the antibacterial activities of double, triple and higher component
combinations, and variations including aPDT, continues to flourish and the likelihood
of further applications in the clinic is high. As well as this, the increased knowledge
of combination treatments with two or more compounds, especially if synergistic,
will be useful in better informing the intentional design of potentially multi-action
single molecule agents. Subsequent chapters will concentrate on such single molecule
design principles, particularly those that incorporate new or untried proposals.
References
Abdali N, Parks JM, Haynes KM et al. (2017) Reviving antibiotics: efflux pump inhibitors that
interact with AcrA, a membrane fusion protein of the AcrAB-TolC multidrug efflux pump. ACS
Infect Dis 3 (1):89–98
Aboulmagd E, Alsultan AA (2014) Synergic bactericidal activity of novel antibiotic combinations
against extreme drug resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Afric J
Microbiol Res 8 (9): 856–861
Abrudan MI, Smakman F, Grimbergen AJ et al. (2015) Socially mediated induction and suppression
of antibiosis during bacterial coexistence. Proc Natl Acad Sci U S A 112 (35):11054–11059
Ammeter D, Idowu T, Zhanel GG et al. (2019) Development of a nebramine-cyclam conjugate as an
antibacterial adjuvant to potentiate β-lactam antibiotics against multidrug-resistant P. aeruginosa.
J Antibiot (Tokyo) 72 (11):816–826
Arrue L, Ratjen L (2017) Internal targeting and external control: Phototriggered targeting in
nanomedicine. ChemMedChem 12:1908–1916
Ball AR, Casadei G, Samosorn S et al. (2006) Conjugating berberine to a multidrug resistance pump
inhibitor creates an effective antimicrobial. ACS Chem Biol 1 (9):594–600
Beppler C, Tekin E, Mao Z et al. (2016) Uncovering emergent interactions in three-way
combinations of stressors. J R Soc Interface 13:20160800
Bezar IF, Mashruwala AA, Boyd JM et al. (2019) Drug-like fragments inhibit agr-mediated virulence
expression in Staphylococcus aureus. Sci Rep 9 (1):6786
Bremner JB, Ambrus JI, Samosorn S (2007) Dual-action based approaches to antibacterial agents.
Curr Med Chem 14(13):1459–1477
Brochado AR, Telzerow A, Bobonis J et al. (2018) Species-specific activity of antibacterial drug
combinations. Nature 559 (7713):259–263
Brown DG, Boström J (2018) Where do recent small molecule clinical development candidates
come from? J Med Chem 61 (21):9442–9468
Brown ED, Wright GD (2016) Antibacterial drug discovery in the resistance era. Nature 529:336–
343
Bush K (2015) Antibiotics: synergistic MRSA combinations. Nat Chem Biol 11 (11):832–833
45
2016 (Vjecha et al. 2018). In theory, extensions to include one or more dual or triple
action hybrids (and/or associated prodrugs) in the five component mixture would
extend the activity profile beyond five separate single actions, but it is considered
less likely to be realised in practice though.
2.2 Summary
The investigation of the antibacterial activities of double, triple and higher component
combinations, and variations including aPDT, continues to flourish and the likelihood
of further applications in the clinic is high. As well as this, the increased knowledge
of combination treatments with two or more compounds, especially if synergistic,
will be useful in better informing the intentional design of potentially multi-action
single molecule agents. Subsequent chapters will concentrate on such single molecule
design principles, particularly those that incorporate new or untried proposals.
References
Abdali N, Parks JM, Haynes KM et al. (2017) Reviving antibiotics: efflux pump inhibitors that
interact with AcrA, a membrane fusion protein of the AcrAB-TolC multidrug efflux pump. ACS
Infect Dis 3 (1):89–98
Aboulmagd E, Alsultan AA (2014) Synergic bactericidal activity of novel antibiotic combinations
against extreme drug resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Afric J
Microbiol Res 8 (9): 856–861
Abrudan MI, Smakman F, Grimbergen AJ et al. (2015) Socially mediated induction and suppression
of antibiosis during bacterial coexistence. Proc Natl Acad Sci U S A 112 (35):11054–11059
Ammeter D, Idowu T, Zhanel GG et al. (2019) Development of a nebramine-cyclam conjugate as an
antibacterial adjuvant to potentiate β-lactam antibiotics against multidrug-resistant P. aeruginosa.
J Antibiot (Tokyo) 72 (11):816–826
Arrue L, Ratjen L (2017) Internal targeting and external control: Phototriggered targeting in
nanomedicine. ChemMedChem 12:1908–1916
Ball AR, Casadei G, Samosorn S et al. (2006) Conjugating berberine to a multidrug resistance pump
inhibitor creates an effective antimicrobial. ACS Chem Biol 1 (9):594–600
Beppler C, Tekin E, Mao Z et al. (2016) Uncovering emergent interactions in three-way
combinations of stressors. J R Soc Interface 13:20160800
Bezar IF, Mashruwala AA, Boyd JM et al. (2019) Drug-like fragments inhibit agr-mediated virulence
expression in Staphylococcus aureus. Sci Rep 9 (1):6786
Bremner JB, Ambrus JI, Samosorn S (2007) Dual-action based approaches to antibacterial agents.
Curr Med Chem 14(13):1459–1477
Brochado AR, Telzerow A, Bobonis J et al. (2018) Species-specific activity of antibacterial drug
combinations. Nature 559 (7713):259–263
Brown DG, Boström J (2018) Where do recent small molecule clinical development candidates
come from? J Med Chem 61 (21):9442–9468
Brown ED, Wright GD (2016) Antibacterial drug discovery in the resistance era. Nature 529:336–
343
Bush K (2015) Antibiotics: synergistic MRSA combinations. Nat Chem Biol 11 (11):832–833