Synthesis, Characterization, and Biological Evaluation of Red Light-Activatable BODIPY-Caged Ceritinib Compounds

Abstract

In this work, we aimed at photocaging the well-known anticancer agents dasatinib, ceritinib, gemcitabine, and combretastatin A4 with red-light activatable 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based cages using a carbonate/carbamate linking strategy. Due to the synthetic challenges discussed in this article, we only obtained two target compounds, namely two caged ceritinib compounds. The latter were characterized in-depth by nuclear magnetic resonance spectroscopy (NMR, ¹H, COSY, ¹³C), high-resolution mass spectrometry (HRMS), infrared (IR) spectroscopy, and their purity was evaluated by elemental analysis. Their photophysical characteristics were also measured including absorption and emission spectra, quantum yields, and lifetimes. Analysis of the products after irradiation of the compounds allowed us to make assumptions about the possible mechanism of the phototransformations. Moreover, we conducted biological studies to determine the phototoxicity indexes of A549 cancer cells. While the two compounds were found to be non-toxic, the BODIPY precursors themselves were found to be highly toxic upon irradiation with phototoxicity indexes up to 1400.