| Autor: |
Ooi N; Infex Therapeutics, Alderley Park, Macclesfield SK10 4TG, UK., Cooper IR; Infex Therapeutics, Alderley Park, Macclesfield SK10 4TG, UK., Norman B; Institute of Life Course and Medical Sciences, William Henry Duncan Building, University of Liverpool, Liverpool L7 8TX, UK., Gallagher JA; Institute of Life Course and Medical Sciences, William Henry Duncan Building, University of Liverpool, Liverpool L7 8TX, UK., Sireau N; AKU Society, Cambridge CB1 2BL, UK., Bou-Gharios G; Institute of Life Course and Medical Sciences, William Henry Duncan Building, University of Liverpool, Liverpool L7 8TX, UK., Ranganath LR; Institute of Life Course and Medical Sciences, William Henry Duncan Building, University of Liverpool, Liverpool L7 8TX, UK.; Departments of Clinical Biochemistry and Metabolic Medicine, Liverpool University Hospitals NHS Foundation Trusts, Liverpool L7 8XP, UK., Savage VJ; Infex Therapeutics, Alderley Park, Macclesfield SK10 4TG, UK. |
| Abstrakt: |
Despite urgent warnings about the spread of multidrug-resistant bacteria, the antibiotic development pipeline has remained sparsely populated. Naturally occurring antibacterial compounds may provide novel chemical starting points for antibiotic development programs and should be actively sought out. Evaluation of homogentisic acid (HGA), an intermediate in the tyrosine degradation pathway, showed that the compound had innate activity against Gram-positive and Gram-negative bacteria, which was lost following conversion into the degradation product benzoquinone acetic acid (BQA). Anti-staphylococcal activity of HGA can be attributed to effects on bacterial membranes. Despite an absence of haemolytic activity, the compound was cytotoxic to human HepG2 cells. We conclude that the antibacterial activity and in vitro safety profile of HGA render it more suitable for use as a topical agent or for inclusion in a small-molecule medicinal chemistry program. |
