Details

Autor(en) / Beteiligte

• Bedernjak, Alexandre F
• Zaytsev, Andrey V
• Babolat, Michèle
• Cellier, Marie
• James, Arthur L
• Orenga, Sylvain
• Perry, John D
• Groundwater, Paul W
• Anderson, Rosaleen J

Titel

Synthesis and Evaluation of Novel 7- and 8‑Aminophenoxazinones for the Detection of β‑Alanine Aminopeptidase Activity and the Reliable Identification of Pseudomonas aeruginosa in Clinical Samples

Ist Teil von

• Journal of medicinal chemistry, 2016-05, Vol.59 (10), p.4476-4487

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• A series of novel 8-aminophenoxazin-3-one and 7-aminophenoxazin-3-one chromogens and their corresponding β-alanine derivatives were synthesized and evaluated for their ability to detect β-alanyl aminopeptidase activity in bacteria known to hydrolyze β-alanine derivatized substrates. The results provided insight into the structural requirements for effective visualization of enzymatic activity and the mechanism of formation of phenoxazinon-3-ones. 8-Aminophenoxazin-3-one substrates 23c, 23d, and 23e were prepared in good to high overall yield and were selective for β-alanyl aminopeptidase activity in bacteria, producing a lighter agar background coloration facilitating visualization of colored colonies, with variable localization to the colonies, but had lower sensitivities for the detection of Pseudomonas aeruginosa in comparison to the analogous 7-aminophenoxazin-3-one substrates. The synthetic methodology employed here allows the preparation of a range of substrates for evaluation and the establishment of structure–activity relationships. For example, the 2-pentyl substituted aminophenoxazin-3-one 22b performed with analogous sensitivity to the corresponding 1-pentyl-7-aminophenoxazin-3-one substrate 1 used commercially, highlighting that the position of the pentyl substituent can be varied while maintaining detection sensitivity.