Estudo in silico da interação entre as enzimas Purina Nucleosídeo Fosforilase e Enoil Redutase do P. falciparum com artemisinina, beta bisaboleno e beta cariofileno

Abstract

Every year millions of people die around the world due to viral, bacterial and parasitic infections. Malaria is the fifth leading cause of death for infectious diseases in the world, after respiratory infections, HIV / AIDS, diarrheal diseases and tuberculosis, with the number of victims 3 times higher than the number of victims of current armed conflicts. Malaria is also known as impaludism, terçã fever, quartã fever, maleita and others. It is caused by parasites of the genus Plasmodium, family Plasmodidae, filo Apicomplexa, with about 156 species that infect several vertebrates, and five of them can infect humans: P. falciparum, P. malarie, P. Vivax, P. Knowlesi and P. Ovale, and malaria caused by P. falciparum is the most severe form of the disease. The increasing resistance of the parasite to antimalarial chemotherapy has worried the medical community and intensified the search for new antimalarial drugs. The purine nucleoside phosphorylase enzyme (PfPNP) catalyzes the formation of hypoxanthine, essential for the purine synthesis pathway. The enzyme enoyl reductase (PfENR), has significant importance in regulating the fatty acid elongation cycle. Beta Cariophilene and Beta Bisabolene are sesquiterpenes found in various plants such as cinnamon (Cinnamomum spp.), Black pepper (Piper nigrum L.), clove (Syzygium aromaticum), cannabis (Cannabis sativa L.) lavender (Lavandula angustifolia), oregano (Origanum vulgare L.), rosemary (Rosmarinus officinalis) Copaíba (copaífera reticulata), and exhibit anti-inflammatory, anticarcinogenic, antimicrobial, antioxidative and analgesic therapeutic properties. In this work, three-dimensional models for the enzymes were constructed from structures obtained in the Protein Data Bank database using Modeller 9.23 software and Verify3D, MolProbity and ModFold validation techniques were used to determine the stereochemical quality of the models. The Molecular Dynamics (DM) of the enzymes and the topology of the ligands were performed using the GROMACS 5.1.4 software package, with the Gromos 96.1 force field (53A6) Calculations of Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and radius of gyration (Rg) were used for comparison and analysis of the systems with binders in relation to the free form. The binding sites of the enzymes with the ligands were obtained with Autodock Vina 1.1.2 and Autodock Tools 1.5.6 molecular docking software. Molecular docking simulations were also carried out with Artemisinin, which is the most recently used treatment for malaria, and with triclosan for PfEACPR, as this is a known inhibitor of this enzyme and with inosine, which is a natural inhibitor of the enzyme PfPNP.