title: Phosphodiesterase inhibitors as a new generation of antiprotozoan drugs: exploiting the benefit of enzymes that are highly conserved between host and parasite.
abstract: Protozoan infections remain a major unsolved medical problem in many parts of our world. A major obstacle to their treatment is the blatant lack of medication that is affordable, effective, safe and easy to administer. For some of these diseases, including human sleeping sickness, very few compounds are available, many of them old and all of them fraught with toxic side effects. We explore a new concept for developing new-generation antiprotozoan drugs that are based on phosphodiesterase (PDE) inhibitors. Such inhibitors are already used extensively in human pharmacology. Given the high degree of structural similarity between the human and the protozoan PDEs, the vast expertise available in the human field can now be applied to developing disease-specific PDE inhibitors as new antiprotozoan drugs.
authors.affiliation: Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH-3012 Bern, Switzerland. thomas.seebeck@izb.unibe.ch
authors.forename: Thomas
authors.initials: T
authors.lastname: Seebeck
authors.forename: Geert Jan
authors.initials: GJ
authors.lastname: Sterk
authors.forename: Hengming
authors.initials: H
authors.lastname: Ke
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites; D020134:Catalytic Domain; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018320:Leishmania major / Q000201:enzymology; D008969:Molecular Sequence Data; D058069:Neglected Diseases / Q000188:drug therapy; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D016415:Sequence Alignment; D014346:Trypanosoma brucei brucei / Q000201:enzymology
chemical_list: D000981:Antiprotozoal Agents; D002396:Catechols; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; C034221:catechol; D015056:1-Methyl-3-isobutylxanthine