Computational Studies on Selected Macrolides Active against <i>Escherichia coli</i> Combined with the NMR Study of Tylosin A in Deuterated Chloroform
Biljana Arsic,
Jill Barber,
Ana Cikos,
Manikandan Kadirvel,
Emilija Kostic,
Andrew J. McBain,
Jelena Milicevic,
Angela Oates,
Andrew Regan
Affiliations
Biljana Arsic
Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
Jill Barber
Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
Ana Cikos
NMR Centre, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
Manikandan Kadirvel
Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
Emilija Kostic
Faculty of Medicine, University of Nis, Bulevar dr Zorana Djindjica 81, 18000 Nis, Serbia
Andrew J. McBain
Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
Jelena Milicevic
Laboratory for Bioinformatics and Computational Chemistry, Vinca Institute of Nuclear Sciences, National Institute of the Republic of Serbia, The University of Belgrade, Mike Petrovica Alasa 12-14, 11351 Belgrade, Serbia
Angela Oates
Centre for Biomedicine, Hull York Medical School, Faculty of Health Sciences, University of Hull, Hull HU6 7RX, UK
Andrew Regan
Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
Although many antibiotics are active against Gram-positive bacteria, fewer also show activity against Gram-negative bacteria. Here, we present a combination of in silico (electron ion-interaction potential, molecular docking, ADMET), NMR, and microbiological investigations of selected macrolides (14-membered, 15-membered, and 16-membered), aiming to discover the pattern of design for macrolides active against Gram-negative bacteria. Although the conformational studies of 14-membered and 15-membered macrolides are abundant in the literature, 16-membered macrolides, and their most prominent representative tylosin A, have received relatively little research attention. We therefore report the complete 1H and 13C NMR assignment of tylosin A in deuterated chloroform, as well as its 3D solution structure determined through molecular modelling (conformational search) and 2D ROESY NMR. Additionally, due to the degradation of tylosin A in deuterated chloroform, other species were also detected in 1D and 2D NMR spectra. We additionally studied the anti-bacterial activity of tylosin A and B against selected Gram-positive and Gram-negative bacteria.
