title: Information-based methods in the development of antiparasitic drugs.
abstract: The discovery and optimization of antiparasitic compounds has profited by information-based methods newly emerged in the modern drug development process. The generation of computer models enables the cost-efficient and fast computational screening of virtual compound libraries for biologically active molecules. Two sources of information are available: structure-based drug design utilizes information about the disease target. We describe two different computational approaches, realized as the fast, flexible docking program FlexX and as the de novo design program LUDI. Ligand-based drug design, on the other hand, requires the structures and experimental data from biologically active compounds. Parasitic targets and antiparasitic compounds studied by various information-based methods include trypanosomal trypanothione reductase, antiprotozoal bisphosphonates, and trypanosomal glycosomal glyceraldehyde-3-phosphate dehydrogenase.
authors.affiliation: 4SC AG, Am Klopferspitz 19a, 82152 Martinsried, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Wolf
authors.forename: Matthias
authors.initials: M
authors.lastname: Dormeyer
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D004164:Diphosphonates / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors / Q000737:chemistry; D008958:Models, Molecular; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D012984:Software; D013095:Spermidine / Q000031:analogs & derivatives* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014345:Trypanosoma / Q000187:drug effects / Q000201:enzymology
chemical_list: D000977:Antiparasitic Agents; D004164:Diphosphonates; D004791:Enzyme Inhibitors; C044809:trypanothione; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005978:Glutathione; D013095:Spermidine