Dinitro Derivative of Naphthalimide as a Fluorescent Probe for Tumor Hypoxia Imaging

Abstract

Fluorescence imaging of tumor hypoxia can potentially offer insights in grading a progressing malignancy, which might subsequently result in metastasis and treatment resistance. Elevated levels of nitroreductase (NTR) have been perceived in hypoxic malignant tumors, and this typical feature was exploited to develop a NTR-targeted probe NNQA to sense hypoxia in vitro through fluorescence imaging. The probe synthesized through imidation of 4-bromo-5-nitro-1,8-naphthalic anhydride and subsequent Suzuki coupling with 4-formylphenylboronic acid displayed a weak blue fluorescence. Electrochemical reduction studies revealed good reducible capacity of probe NNQA. The NTR mediated reduction of NNQA in presence of nicotinamide adenine dinucleotide formed the reduction product with intense green emission. Endogenous NTR-mediated transformation of blue emitting molecular probe NNQA to intensely green fluorescent reduction product was evident in the in vitro cell culture experiments.

Graphical Abstract

Keywords:

• Fluorescent probe
• hypoxia
• naphthalimide
• nitroreductase

CECRI Manuscript Communication Number

CECRI/PESVC/Pubs./2021-152

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work is a part of the PhD thesis of RK. DS and NVA acknowledge the financial support from Department of Atomic Energy (DAE), Board of Research in Nuclear Sciences (BRNS) with sanction number 37(2)/14/01/2018-BRNS/37001.