Bistacrines as potential antitrypanosomal agents

• Verfasst von: Schmidt, Ines [VerfasserIn]
• Verfasst von: Göllner, Sarah [VerfasserIn]
• Verfasst von: Miliu, Alexandra [VerfasserIn]
• Verfasst von: Krauth-Siegel, Renate [VerfasserIn]
• Titel: Bistacrines as potential antitrypanosomal agents
• Verf.angabe: Ines Schmidt, Sarah Göllner, Antje Fuß, August Stich, Anna Kucharski, Tanja Schirmeister, Elena Katzowitsch, Heike Bruhn, Alexandra Miliu, R. Luise Krauth-Siegel, Ulrike Holzgrabe
• E-Jahr: 2017
• Jahr: 1 July 2017
• Umfang: 6 S.
• Fussnoten: Gesehen am 23.05.2018
• Titel Quelle: Enthalten in: Bioorganic & medicinal chemistry
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1993
• Jahr Quelle: 2017
• Band/Heft Quelle: 25(2017), 16, Seite 4526-4531
• ISSN Quelle: 1464-3391
• DOI: doi:10.1016/j.bmc.2017.06.051
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Antitrypanosomal drugs
• Sach-SW: Bistacrine
• Sach-SW: Rhodesain
• Sach-SW: Trypanothione reductase
• K10plus-PPN: 1575423758

Abstract

Human African Trypanosomiasis (HAT) is caused by two subspecies of the genus Trypanosoma, namely Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. The disease is fatal if left untreated and therapy is limited due to only five non-adequate drugs currently available. In preliminary studies, dimeric tacrine derivatives were found to inhibit parasite growth with IC50-values in the nanomolar concentration range. This prompted the synthesis of a small, but smart library of monomeric and dimeric tacrine-type compounds and their evaluation of antiprotozoal activity. Rhodesain, a lysosomal cathepsin-L like cysteine protease of T. brucei rhodesiense is essential for parasite survival and likely target of the tacrine derivatives. In addition, the inhibition of trypanothione reductase by bistacrines was found. This flavoprotein oxidoreductase is the main defense against oxidative stress in the thiol redox system unique for protozoa.