Computational Studies on Selected Macrolides Active against Escherichia coli Combined with the NMR Study of Tylosin A in Deuterated Chloroform

Arsic, Biljana; Barber, Jill; Cikos, Ana; Kadirvel, Manikandan; Kostic, Emilija; McBain, Andrew; Milicevic, Jelena; Oates, Angela; Regan, Andrew

Abstract

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.

Citation

Arsic, B., Barber, J., Cikos, A., Kadirvel, M., Kostic, E., McBain, A., …Regan, A. (2022). Computational Studies on Selected Macrolides Active against Escherichia coli Combined with the NMR Study of Tylosin A in Deuterated Chloroform. Molecules, 27(21), Article 7280. https://doi.org/10.3390/molecules27217280

• Journal Article Type: Article
• Acceptance Date: Oct 22, 2022
• Online Publication Date: Oct 26, 2022
• Publication Date: Nov 1, 2022
• Deposit Date: Oct 26, 2022
• Publicly Available Date: Oct 27, 2022
• Journal: Molecules
• Electronic ISSN: 1420-3049
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 27
• Issue: 21
• Article Number: 7280
• DOI: https://doi.org/10.3390/molecules27217280
• Keywords: Macrolides; Bacteria; 2D ROESY NMR
• Public URL: https://hull-repository.worktribe.com/output/4104948