Synthesis of Triazole Derivatives of Pillar[5]arene and Their Self-Assembly with Antitumor Fluoropyrimidine Drugs

Abstract For the first time, water-soluble triazole derivatives of pillar[5]arene were synthesized. UV-Vis spectroscopy has revealed the formation of associates between pillar[5]arenes with 1,2,3-thiotriazole moieties and antitumor fluoropyrimidine drugs in a macrocycle : drug = 1 : 2 stoichiometric ratio in water. The association constant of the macrocycle with 5-fluorouracil was 5.46 and with floxuridine it was 7.04. Dynamic light scattering demonstrated the self-assembly of the macrocycle containing 1,2,4-thiotriazole fragments into stable associates in water, with a size of 180 nm over the entire concentration range studied (1–100 μM), in contrast to the isomeric pillar[5]arene. The critical aggregation concentration (CAC) for the macrocycle with 1,2,4-thiotriazole was 43 μM and for the pillar[5]arene with 1,2,3-thiothiothriazole it was 110 μM. At the same time, both macrocycles did not show toxicity towards model adenocarcinoma cells (A549) in vitro.