Stereospecific synthesis of chiral 2,3-dihydro-1,4-benzodithiine and methyl-2,3-dihydro-1,4-benzodithiine derivatives and their toxic effects on Trypanosoma brucei.
Preparation of chiral 2,3-dihydro-1,4-benzodithiine and methyl-2,3-dihydro-1,4-benzodithiine derivatives with known absolute configurations from the easily accessible chiral synthons benzyl 4-O-trifloxy-2,3-anhydro-beta-L-ribopyranoside and benzyl 4-O-trifloxy-2,3-anhydro-alpha-D-ribopyranoside is described. These compounds showed significant in vitro toxicity of the bloodstream form of Trypanosoma brucei with an IC50 of 11 microM. The parasites' energy metabolism and consumption of oxygen were found to be affected during incubation.
Ali Shah
Syed Tasadaque
ST
Physiologisch-chemisches Institut der Universität Tübingen, Hoppe-Seyler Strasse 4, 72076 Tübingen, Germany.
Merkel
Patrick
P
Ragge
Hubert
H
Duszenko
Michael
M
Rademann
Jörg
J
Voelter
Wolfgang
W
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D021261:Parasitic Sensitivity Tests; D013237:Stereoisomerism; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
D006575:Heterocyclic Compounds, 3-Ring; D014344:Trypanocidal Agents; C504686:methyl-2,3-dihydro-1,4-benzodithiine