title: Computer-aided molecular design of novel glucosidase inhibitors for AIDS treatment.
abstract: Since the onset of the AIDS epidemic, some 20 million people have died and the estimate is that today close to 40 million are living with type 1 human immunodeficiency virus (HIV)/AIDS. About 14 thousands people are infected worldwide daily with this disease. Still, only a few pharmaceuticals are available for AIDS chemotheraphy. Some pharmaceuticals act against the virus before the entrance of the HIV into the host cells. One of these targets is the glucosidase protein. This class of enzymes has been recently explored because the synthesis of viral glycoproteins depends on the activity of enzymes, such as glucosidase and transferase, for the elaboration of the polysaccharides. In this work we study several glucosidase inhibitors. The DFT method is used to compute atomic charges and the ligand/receptor interaction was simulated with docking software. Analysis of the interactions of the proposed pharmaceutical, a pseudodisaccharide, with the Thermotoga maritima 4-alpha-glucanotransferase in complex with modified acarbose, the scores from docking as well as the graphical superposition of all the ligands, suggest that our molecular designed pseudo-disaccharide may be a potent glucosidase inhibitor.
authors.affiliation: Departamento de Ciências Farmaceuticas Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de Sao Paulo, Av. do Cafe, s/n, Monte Alegre, 14040-903, Ribeirão Preto, Brasil.
authors.forename: C H T P
authors.initials: CH
authors.lastname: Silva
authors.forename: C A
authors.initials: CA
authors.lastname: Taft
mesh_terms: D020909:Acarbose / Q000378:metabolism; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000627:therapeutic use; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D006004:Glycogen Debranching Enzyme System / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular
chemical_list: D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D006004:Glycogen Debranching Enzyme System; C020569:4 alpha-glucanotransferase; D005959:Glucosidases; D020909:Acarbose