AUTHOR=Odyniec Maria L. , Han Hai-Hao , Gardiner Jordan E. , Sedgwick Adam C. , He Xiao-Peng , Bull Steven D. , James Tony D. TITLE=Peroxynitrite Activated Drug Conjugate Systems Based on a Coumarin Scaffold Toward the Application of Theranostics JOURNAL=Frontiers in Chemistry VOLUME=7 YEAR=2019 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2019.00775 DOI=10.3389/fchem.2019.00775 ISSN=2296-2646 ABSTRACT=

Two novel drug-conjugates based on a “coumarin linker” have been designed for the synergic release of a therapeutic agent and fluorescent probe for the potential application of theranostics. The drug conjugates; CC-RNS and CI-RNS were designed to be activated by reactive oxygen species or reactive nitrogen species (ROS/RNS). The fluorescence OFF-ON response was triggered by the peroxynitrite-mediated transformation of a boronic acid pinacol ester to a phenol moiety with simultaneous release of the therapeutic agents (Confirmed by HRMS). The limit of detection for peroxynitrite using CC-RNS and CI-RNS was 0.29 and 37.2 μM, respectively. Both CC-RNS and CI-RNS demonstrated the ability to visualize peroxynitrite production thus demonstrating the effectiveness of these probes for use as tools to monitor peroxynitrite-mediated drug release in cancer cell lines.