Synthesis and in vivo proof of concept of a BODIPY-based fluorescent probe as a tracer for biodistribution studies of a new anti-Chagas agent

Abstract

The potential use of amide-containing thiazoles, especially (2E,2Z)-3-allyl-4-[((E)-4-cinnamylpiperazin-1-yl)carbonyl]-2-[2-((E)-3-(furan-2-yl)propenylidene)hydrazono]-2,3-dihydrothiazole (1), as drugs for the treatment of Chagas disease has been recently described. The therapeutic application of 1 requires further pre-clinical studies, including in vivo biodistribution. In this sense, a BODIPY-fluorophore based probe for this drug (1-BODIPY) was developed and investigated for its potential as an in vivo tracer. The fluorescent tracer was synthesized, physicochemically and in vitro biologically characterised, and its in vivo biodistribution evaluated. The in vitro studies demonstrated that the fluorescent probe could simulate the in vivo behaviour of compound 1. Furthermore, the in vivo proof of concept showed that the 1-BODIPY biodistribution involves organs that are associated with the parasitic disease. These findings allow us to establish future administration routes and regimens in the treatment of Chagas disease with 1.