The QSAR and docking calculations of fullerene derivatives as HIV-1 protease inhibitors

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Vol. 136; pp. 1523 - 1529
• Main Author: Saleh, Noha A.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05.02.2015
• Subjects: Catalytic Domain; Docking; Drug Design; Fullerene; Fullerenes - chemistry; HIV Protease Inhibitors - chemistry; HIV-1 protease inhibitors; Hydrophobic and Hydrophilic Interactions; Hydroxymethylcarbonyl group; Models, Molecular; Molecular Docking Simulation; Molecular Structure; PM3; QSAR; Quantitative Structure-Activity Relationship; Fullerene; Hydroxymethylcarbonyl group; Docking; HIV-1 protease inhibitors; QSAR; PM3
• ISSN: 1386-1425; 1873-3557
• DOI: 10.1016/j.saa.2014.10.045

The fullerene diameter is similar to the diameter of HIV-1 protease and form good hydrophobic interaction with the hydrophobic residues in HIV-1 protease. Unfortunately, the fullerene is insoluble in biological system. In this study some fullerene derivatives are modified to increase the solubility and inhibitory properties. These properties studied through QSAR and docking calculations. According to this study the fullerene derivative with two O atoms+HMC groups has good HIV-1 protease inhibitory properties. This result is benefit to improve the treatment of AIDS. [Display omitted] •Fullerene derivatives as HIV-1 protease inhibitors.•Quantitative Structure Activity Relationship (QSAR).•Docking calculations. The inhibition of HIV-1 protease is considered as one of the most important targets for drug design and the deactivation of HIV-1. In the present work, the fullerene surface (C60) is modified by adding oxygen atoms as well as hydroxymethylcarbonyl (HMC) groups to form 6 investigated fullerene derivative compounds. These compounds have one, two, three, four or five O atoms+HMC groups at different positions on phenyl ring. The effect of the repeating of these groups on the ability of suggested compounds to inhibit the HIV protease is studied by calculating both Quantitative Structure Activity Relationship (QSAR) properties and docking simulation. Based on the QSAR descriptors, the solubility and the hydrophilicity of studied fullerene derivatives increased with increasing the number of oxygen atoms+HMC groups in the compound. While docking calculations indicate that, the compound with two oxygen atoms+HMC groups could interact and binds with HIV-1 protease active site. This is could be attributed to the active site residues of HIV-1 protease are hydrophobic except the two aspartic acids. So that, the increase in the hydrophilicity and polarity of the compound is preventing and/or decreasing the hydrophobic interaction between the compound and HIV-1 protease active site.