A Comprehensive Cheminformatics Analysis of Structural Features Affecting the Binding Activity of Fullerene Derivatives.

Natalja Fjodorova,Marjana Novič,Bakhtiyor Rasulev,Katja Venko

doi:10.3390/nano10010090

Natalja Fjodorova, Marjana Novič + Show 2 more

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https://doi.org/10.3390/nano10010090

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Abstract

Nanostructures like fullerene derivatives (FDs) belong to a new family of nano-sized organic compounds. Fullerenes have found a widespread application in material science, pharmaceutical, biomedical, and medical fields. This fact caused the importance of the study of pharmacological as well as toxicological properties of this relatively new family of chemicals. In this work, a large set of 169 FDs and their binding activity to 1117 disease-related proteins was investigated. The structure-based descriptors widely used in drug design (so-called drug-like descriptors) were applied to understand cheminformatics characteristics related to the binding activity of fullerene nanostructures. Investigation of applied descriptors demonstrated that polarizability, topological diameter, and rotatable bonds play the most significant role in the binding activity of FDs. Various cheminformatics methods, including the counter propagation artificial neural network (CPANN) and Kohonen network as visualization tool, were applied. The results of this study can be applied to compose the priority list for testing in risk assessment related to the toxicological properties of FDs. The pharmacologist can filter the data from the heat map to view all possible side effects for selected FDs.

Highlights

Fullerene derivatives (FDs) are a relatively new class of organic compounds belonging to nano-sized materials
At the same time, when fullerenes are exposed to a light, they can initiate formation of reactive oxygen species (ROS), which leads to antibacterial/antimicrobial activity, and this effect of fullerene derivatives (FDs) is used in water treatment systems [11,15,16,17,18,19]
The classification of FDs dependent on the type of bond related to substituent group attached to the fullerene C60 core is represented in Tables S2–S8

Summary

Introduction

Fullerene derivatives (FDs) are a relatively new class of organic compounds belonging to nano-sized materials. These materials have opened up new opportunities in nanotechnology, as well as in medicine [1]. The radical scavenging properties of fullerenes have found many applications in biological systems. They were applied for treatment of various free radical-induced biological disorders, including mostly neurodegenerative diseases (i.e., amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease) and other cytotoxic processes caused by oxidative stress. At the same time, when fullerenes are exposed to a light, they can initiate formation of ROSs (singlet oxygen and superoxide), which leads to antibacterial/antimicrobial activity, and this effect of FDs is used in water treatment systems [11,15,16,17,18,19]

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