Ooi, Nicola, Cooper, Ian R, Norman, Brendan 
ORCID: 0000-0001-9293-4852, Gallagher, James A, Sireau, Nick, Bou-Gharios, George, Ranganath, Lakshminarayan R and Savage, Victoria J
(2023)
Evaluation of Homogentisic Acid, a Prospective Antibacterial Agent Highlighted by the Suitability of Nitisinone in Alkaptonuria 2 (SONIA 2) Clinical Trial.
CELLS, 12 (13).
1683-.
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | alkaptonuria, AKU, homogentisic acid, antimicrobial, bacteria, safety, mechanism of action |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 11 Jul 2023 15:21 |
| Last Modified: | 09 Aug 2023 12:59 |
| DOI: | 10.3390/cells12131683 |
| Open Access URL: | https://www.mdpi.com/2073-4409/12/13/1683 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3171631 |
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