Arsic, B

Barber, J

McBain, A

Morris, G

Oates, A

Regan, A

Oates, Angela

Arsic, Biljana

Regan,  Andrew

Morris, Gareth

McBain,  Andrew

Barber, Jill

Repository@Hull - Worktribe

Conformational studies of tylosin A, tylosin B, erythromycin B and erythromycin C and full assignments of tylosin A in CDCl3 and tylosin B in phosphate buffered D2O

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This is a repository copy of Conformational studies of tylosin A, tylosin B, erythromycin B and erythromycin C and full assignments of tylosin A in CDCl3 and tylosin B in phosphate buffered D2O.White Rose Research Online URL for this paper:http://eprints.whiterose.ac.uk/129796/Version: Published VersionConference or Workshop Item:Arsic, B, Regan, A, Morris, G et al. (3 more authors) (2017) Conformational studies of tylosin A, tylosin B, erythromycin B and erythromycin C and full assignments of tylosin A in CDCl3 and tylosin B in phosphate buffered D2O. In: 1st RSC Anglo-Nordic Medicinal Chemistry Symposium, 11-14 Jun 2017. (Unpublished) eprints@whiterose.ac.ukhttps://eprints.whiterose.ac.uk/Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. Conformational studies of tylosin A, tylosin B, erythromycin B and erythromycin C and full assignments of tylosin A in CDCl3 and tylosin B in phosphate buffered D2OBiljana Arsic1, Andrew Regan2, Gareth Morris2, Angela Oates1, Andrew McBain1, Jill Barber11 Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Oxford Road, M13 9PT, Manchester, UK2 School of Chemistry, University of Manchester, Oxford road, M13 9PL, Manchester, UKIntroductionErythromycins and tylosins show similar instability in aqueous solution, so theyare worthy of investigation and comparison. Tylosin A decomposes into tylosin BResults and DiscussionThe global minimum for tylosin B in H2O found using Macromodel software wassimilar to that previously found for tylosin A (Arsic et al., 2017) (Figure 2A), and itsl b l i i i ith f ld d t f ld d i f ti E th i B tP01in acid (Figure 1 A). Erythromycin A is in equilibrium with its hemiacetal form, anddecomposes easily in the acid medium (Figure 1B). Erythromycins B and C weresynthesized in order to increase acid stability while keeping a similar spectrum ofantimicrobial activity to erythromycin A (Figure 1C).g o a m n mum s ne er o e -ou nor o e - n con orma on. ry romyc n aits global minimum (E = 143.86 kJ mol-1) adopts a folded-in conformation, anderythromycin C (E = 73.48 kJ mol-1) a folded-out conformation similar toerythromycin A (Figure 2B). Each global minimum was found multiple times.Minimum inhibitory concentrations for tylosin A and tylosin B were lower than forclarithromycin and azithromycin (Table 1), as expected, based on our earlierfindings connected to the relation between the conformation of the global minimumBand the spectrum of anti-bacterial activities (Arsic et al., 2014).Full assignments for the 1H and 13C spectra of tylosin A in CDCl3 and tylosin B inphosphate buffered D2O were achieved.A BFigure 2. Global minima for A Tylosin A in CHCl3; B Erythromycin B anderythromycin C.Bacterial strains MIC (µg mL-1)CFigure 1. A Tylosin A and its decomposition product in the acid medium-tylosin B; B Erythromycin A and its degradation products; C ErythromycinB and erythromycin C.Materials and MethodsMolecular modellingConformational searching of tylosin B, erythromycin B and C in water was Clarithromycin Azithromycin Tylosin A Tylosin BEscherichia coli wound isolate 12 2 125 31.25Bacillus cereus MRBG 4.21 0.2 4 0.98 0.98Staphylococcus aureus wound isolate 0.2 8 31.25 >500Pseudomonas aeruginosa PA01 62.5 15.6 250 62.5Staphylococcus epidermidis clinical isolate 250 31.2 250 62.5Serratia marcescens wound isolate >500 >500 500 250Corynebacterium xerosis wound isolate >500 250 500 250performed using Macromodel software.NMR analysisFull spectral assignments of tylosin A in CDCl3 and tylosin B in phosphatebuffered D2O were achieved using a combination of 1D and 2D NMR techniques :1H, 13C, DEPT90, DEPT135, COSY, HSQC and HMBC.Determination of Minimum Inhibitory Concentrations (MIC)ConclusionsThe antibacterial activities of tylosin A and tylosin B found for the bacterialstrains studied are lower than those found for clarithromycin and azithromycin.Thi i i t t ith th l b l i i f ti f th t l iTable 1. Minimum inhibitory concentrations (MICs) expressed in µg mL-1 fortylosin A and tylosin B compared to clarithromycin and azithromycinReferences B. Arsic, J. A. Aguilar, R. A. Bryce, J. Barber, Magn. Reson. Chem. 2017, 55(4), 367-373.B. Arsic, A. Awan, R. J. Brennan, J. A. Aguilar, R. Ledder, A. J. McBain, A. C. Regan, J. Barber, Med. Chem. Commun. 2014,5, 1347-1354.A.J. McBain, R. G. Ledder, P. Sreenivasan, P. Gilbert, J. Antimicrob. Chemother. 2004, 53(5), 772-777.Minimum Inhibitory Concentrations (MICs) were determined using standardmethods (McBain et al., 2004).s s cons s en w e g o a m n mum con orma ons o e y os nsinvestigated, which are neither folded-out nor folded-in.

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Conformational studies of tylosin A, tylosin B, erythromycin B and erythromycin C and full assignments of tylosin A in CDCl3 and tylosin B in phosphate buffered D2O

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