67097-22-7Relevant academic research and scientific papers
Semisynthesis and biological evaluation of a focused library of unguinol derivatives as next-generation antibiotics
Morshed, Mahmud T.,Nguyen, Hang T.,Vuong, Daniel,Crombie, Andrew,Lacey, Ernest,Ogunniyi, Abiodun D.,Page, Stephen W.,Trott, Darren J.,Piggott, Andrew M.
, p. 1022 - 1036 (2021)
In this study, we report the semisynthesis andin vitrobiological 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 vitroantibacterial 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-resistantStaphylococcus aureus(MIC 0.25-1 μg mL?1) and are promising candidates for further developmentin vivo.
