Fluorescein-Labeled Thiacalix[4]arenes as Potential Theranostic Molecules: Synthesis, Self-Association, and Antitumor Activity.

In this paper, a series of thiacalix[4]arenes were synthesized as potential theranostic molecules for antitumor therapy. We propose an original strategy for the regioselective functionalization of thiacalix[4]arene with a fluorescent label to obtain antiangiogenic agent mimetics. The aggregation properties of the synthesized compounds were determined using the dynamic light scattering. The average hydrodynamic diameter of self-associates formed by the macrocycles in 1,3-alternate conformation is larger (277-323 nm) than that of the similar macrocycle in cone conformation (185-262 nm). The cytotoxic action mechanism of the obtained compounds and their ability to penetrate into of human lung adenocarcinoma and human duodenal adenocarcinoma cells were established using the MTT-test and flow cytometry. Thiacalix[4]arenes in 1,3-alternate conformation did not have a strong toxic effect. The toxicity of macrocycles in cone conformations on HuTu-80 and A549 cells (IC 50 = 21.83-49.11 µg/mL) is shown. The resulting macrocycles are potential theranostic molecules that combine both the pharmacophore fragment for neoplasmas treatment and the fluorescent fragment for monitoring the delivery and biodistribution of nanomedicines.