Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase.
Novel quinazoline-type compounds were designed as inhibitors of the parasite specific enzyme trypanothione reductase (TR), and their biological activities were evaluated. Some of our compounds inhibited TR, showed selectivity for TR over human glutathione reductase, and inhibited parasite growth in vitro. We propose that the quinazoline framework is a privileged structure that can be purposely modified to design novel TR inhibitors. Furthermore, the use of privileged motifs might emerge as an innovative approach to antiparasitic lead candidates.
Department of Pharmaceutical Sciences, Alma Mater Studiorum-Bologna University, Bologna, Italy.
Andrea
A
Cavalli
Federica
F
Lizzi
Salvatore
S
Bongarzone
Reto
R
Brun
R
R
Luise Krauth-Siegel
Maria Laura
ML
Bolognesi
D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects
D000977:Antiparasitic Agents; D004791:Enzyme Inhibitors; D011799:Quinazolines; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005980:Glutathione Reductase