A coelenterazine-type bioluminescent probe for nitroreductase imaging.

Abstract

Novel coelenterazine-type bioluminescent probes have been designed and synthesized to detect nitroreductase (NTR) in hypoxic tumors. The design strategy is that NTR catalyzes the reduction of the nitrobenzyl moiety to the aniline group with an electron donor, thus resulting in 1,4 or 1,6-rearrangement-elimination to release coelenterazine analogues, which can be catalyzed by Renilla luciferase to emit bioluminescence. After careful evaluation, almost all probes had a 3-fold greater response for NTR over other biologically relevant substances at >100-fold dose more than NTR. In the dose-independent and selectivity study, probes A1, A2 and A5 presented a high selectivity in a dose-dependent manner. Overall, among all molecules, probe A5 showed high sensitivity, low cytotoxicity and good compatibility, so as to be successfully applied for assessing the hypoxic status in cellulo and in vivo as the first coelenterazine-type bioluminescent probe.

• Authors: Xingye Yang, Zhenzhen Li, Tianyu Jiang, Lupei Du, Minyong Li
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 16 Issue 1 Pg. 146-151 (Dec 19 2017) ISSN: 1477-0539 [Electronic] England
• PMID: 29218345 (Publication Type: Journal Article)

Chemical References

• Fluorescent Dyes
• Imidazoles
• Pyrazines
• coelenterazine
• Nitroreductases

Topics

• Dose-Response Relationship, Drug
• Fluorescent Dyes (chemical synthesis, chemistry)
• Humans
• Imidazoles (chemical synthesis, chemistry)
• Molecular Structure
• Nitroreductases (analysis, metabolism)
• Pyrazines (chemical synthesis, chemistry)
• Structure-Activity Relationship
• Tumor Cells, Cultured