A Computational Study of the Immobilization of New 5-Nitroisatine Derivatives with the Use of C60-Based Functionalized Nanocarriers

Abstract

Isatin-based compounds are a large group of drugs used as competitive inhibitors of ATP. The 5-nitroisatin derivatives studied in this work are inhibitors of the CDK2 enzyme, which can be used in the development of new anti-cancer therapies. One of the basic activities that often allows for an increase in biological activity while reducing the undesirable effects associated with the toxicity of medicinal substances is immobilization based on carriers. In this work, fifty nanocarriers derived from C60 fullerene, containing a bound phenyl ring on their surfaces, were used in the process of the immobilization of isatin derivatives. Based on flexible docking methods, the binding capacities of the drugs under consideration were determined using a wide range of nanocarriers containing symmetric and asymmetric modifications of the phenyl ring, providing various types of interactions. Based on the data collected for each of the tested drugs, including the binding affinity and the structure and stability of complexes, the best candidates were selected in terms of the type of substituent that modified the nanoparticle and its location. Among the systems with the highest affinity are the dominant complexes created by functionalized fullerenes containing substituents with a symmetrical location, such as R2-R6 and R3-R5. Based on the collected data, nanocarriers with a high potential for immobilization and use in the development of targeted therapies were selected for each of the tested drugs.