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https://hdl.handle.net/2440/130161
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Type: | Journal article |
Title: | Semisynthesis and biological evaluation of a focused library of unguinol derivatives as next-generation antibiotics |
Author: | Morshed, M.T. Nguyen, H.T. Vuong, D. Crombie, A. Lacey, E. Ogunniyi, A.D. Page, S.W. Trott, D.J. Piggott, A.M. |
Citation: | Organic and Biomolecular Chemistry, 2021; 19(5):1022-1036 |
Publisher: | Royal Society of Chemistry |
Issue Date: | 2021 |
ISSN: | 1477-0520 1477-0539 |
Statement of Responsibility: | Mahmud T. Morshed, Hang T. Nguyen, Daniel Vuong, Andrew Crombie, Ernest Lacey, Abiodun D. Ogunniyi, Stephen W. Page, Darren J. Trott and Andrew M. Piggott |
Abstract: | In this study, we report the semisynthesis and in vitro biological evaluation of thirty-four derivatives of the fungal depsidone antibiotic, unguinol. Initially, the semisynthetic modifications were focused on the two free hydroxy groups (3-OH and 8-OH), the three free aromatic positions (C-2, C-4 and C-7), the butenyl side chain and the depsidone ester linkage. Fifteen first-generation unguinol analogues were synthesised and screened against a panel of bacteria, fungi and mammalian cells to formulate a basic structure activity relationship (SAR) for the unguinol pharmacophore. Based on the SAR studies, we synthesised a further nineteen second-generation analogues, specifically aimed at improving the antibacterial potency of the pharmacophore. In vitro antibacterial activity testing of these compounds revealed that 3-O-(2-fluorobenzyl)unguinol and 3-O-(2,4-difluorobenzyl)unguinol showed potent activity against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MIC 0.25–1 μg mL⁻¹) and are promising candidates for further development in vivo. |
Keywords: | Cell Line Animals Heterocyclic Compounds, 3-Ring Anti-Bacterial Agents Microbial Sensitivity Tests Drug Evaluation, Preclinical Methicillin-Resistant Staphylococcus aureus Chemistry Techniques, Synthetic |
Rights: | This journal is © The Royal Society of Chemistry 2021 |
DOI: | 10.1039/d0ob02460k |
Grant ID: | http://purl.org/au-research/grants/arc/FT130100142 |
Published version: | http://dx.doi.org/10.1039/d0ob02460k |
Appears in Collections: | Animal and Veterinary Sciences publications Aurora harvest 8 |
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