Ponente
Descripción
One of the most significant applications of fullerenes is its potential use in biological systems. In the search for fullerene derivatives that could present a greater solubility in biological media to be used in biomedicine. In that sense, employing the Bingel-Hirsch methodology,[1] our group has reported the synthesis of systems based on fullerenes with different molecules such as heterocycles and steroids.[2] The molecular interaction of these compounds with the HIV-1 and SARS-CoV-2 proteases as receptors, open the door for the potential application of these structures in biomedicine as antivirals agents.
In agreement with the previous results, in this work, we report the synthesis of novel steroid-monosaccharide-methano[60]fullerenes with potential biological applications. In addition, the electrochemical properties, thermal stability, deep structural analysis, and chemical-physical properties were studied through theoretical calculations. These hybrids form well-defined spherical nanoparticles in water clustered into different populations according to their size. Some stereoelectronic parameters were calculated to determine the electronic interactions present in these hybrid molecules. Besides, molecular docking was carried out prior optimization of the structures by the theoretical DFT-PBE method and 6-311G(d,p) basis set, to estimate the potential application of the hybrids as HIV-1 protease inhibitors. The C60 cage exhibited interactions with the HIV-1 protease active residues through π–π and π-anion interactions. Furthermore, it was observed that the steroids and monosaccharides moieties formed H-bonds with the residues in the active site of SARS-CoV-2 protease. Protein-ligand docking revealed several important molecular fragments that are responsible for the interaction, thus paving the way to study the possible application of these hybrids in medicinal chemistry.
References
- Y. N. Biglova, A. G. Mustafina, Nucleophilic cyclopropanation of [60]fullerene by the addition–elimination mechanism, RSC Adv. 2019, 9, 22428–22498.
- a) R. Lemos, F. Ortiz, L. Almagro, K. Makowski, N. Martín, F. Albericio, M. Suarez, H. Rodriguez, Morphological behavior of fullerene-steroid hybrid derivatives, Surf. Interface Anal. 2022, 10, 1041-1051; b) L. Almagro, R. Lemos, K. Makowski, H. Rodríguez, O. Ortiz, W. Cáceres, M. Á. Herranz, D. Molero, R. Martínez, M. Suárez, N. Martín, [60]Fullerene Hybrids Bearing “Steroid Wings”: A Joined Experimental and Theoretical Investigation, Eur. J. Org. Chem. 2020, 2020, 5926–5937.
