2-Arylbenzothiazole, benzoxazole and benzimidazole derivatives as fluorogenic substrates for the detection of nitroreductase and aminopeptidase activity in clinically important bacteria

• Published in: Bioorganic & medicinal chemistry 2011-05, Vol.19 (9), p.2903-2910
• Main Authors: Cellier, Marie, Fabrega, Olivier J., Fazackerley, Elizabeth, James, Arthur L., Orenga, Sylvain, Perry, John D., Salwatura, Vindhya L., Stanforth, Stephen P.
• Format: Article
• Language: English
• Subjects: alanine; Aminopeptidase; Aminopeptidases - chemistry; Aminopeptidases - metabolism; Bacteria - enzymology; Bacteria - isolation & purification; Bacteria detection; Bacteriological methods and techniques used in bacteriology; Bacteriology; Benzimidazole; Benzimidazoles; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Benzothiazoles; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; Benzothiazoles - pharmacology; Benzoxazoles; Benzoxazoles - chemical synthesis; Benzoxazoles - chemistry; Benzoxazoles - pharmacology; Biological and medical sciences; chemistry; Colonies; Fluorescence; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Fluorescent Dyes - pharmacology; Fluorgenic substrates; Fundamental and applied biological sciences. Psychology; Gram-negative bacteria; Gram-positive bacteria; L-Alanine; Microbiology; Nitroreductase; Nitroreductases - chemistry; Nitroreductases - metabolism; Substrate Specificity
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2011.03.043

A series of 2-(2-nitrophenyl)benzothiazole 7, 2-(2-nitrophenyl)benzoxazole 10 and 2-(2-nitrophenyl)benzimidazole 13 derivatives have been synthesised and assessed as indicators of nitroreductase activity across a range of clinically important Gram negative and Gram positive bacteria. The majority of Gram negative bacteria produced strongly fluorescent colonies with substrates 7 and 10 whereas fluorescence production in Gram positive bacteria was less widespread. The l-alanine 16 and 19 and β-alanine 21 and 23 derivatives have been prepared from 2-(2-aminophenyl)benzothiazole 14 and 2-(2-aminophenyl)benzoxazole 17. These four compounds have been evaluated as indicators of aminopeptidase activity. The growth of Gram positive bacteria was generally inhibited by these substrates but fluorescent colonies were produced with the majority of Gram negative bacteria tested.