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., Milicevic, J., Oates, 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