Peroxynitrite Activated Drug Conjugate Systems Based on a Coumarin Scaffold Toward the Application of Theranostics

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; <b>CC-RNS</b> and <b>CI-RNS</b> 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 <b>CC-RNS</b> and <b>CI-RNS</b> was 0.29 and 37.2 μM, respectively. Both <b>CC-RNS</b> and <b>CI-RNS</b> 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.