Anthrarufin as reverse transcriptase (rt)inhibitor and potential inhibitor of hiv replication

Abstract

During the 1990s, it was discovered that quinones with one, two, and three aromatic rings are a class of micromolar non-peptidic inhibitors of HIV-1 protease, an enzyme essential for replication of the HIV (Human Immunodeficiency Virus) and an important drug target for AIDS (Acquired immunodeficiency syndrome). It was later observed that simple hydroxyquinones inhibit HIV-1 protease at the micromolar level, which represented a promising goal for the development of HIV drugs. Anthrarufin (1,5-dihydroxy-9,10- anthraquinone) is an anthraquinone already recognized as a molecule with antimalaric and moderate antioxidative activity. In this paper, the molecular interactions between active binding sites of the HIV-1 reverse transcriptase (RT) and anthrarufin were investigated by molecular docking simulations. The binding site of the mentioned protein is defined using AGFR software. The three-dimensional crystal structure of HIV-1 RT is downloaded from the Protein Data Bank (PDB ID: 4RW9). The molecular docking simulations are carried out with (E)-3-(3-chloro-5-(2-(2-(2,4-dioxo-3,4- dihydropyrimidin1(2H)yl)ethoxy)phenoxy)phenyl)acrylonitrile (JLJ532), a non-nucleoside inhibitor, dolutegravir, nevirapine and anthrarufin, as ligands. The molecular docking simulation is performed using the AutoDock 4.0 software. According to the obtained values of free energy of binding (ΔGbind) and inhibition constant (Ki) antrarufin can be considered as a potential inhibitor of HIV-1 RT, since it possesses similar inhibitory potency as examined drugs.