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
Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase / Cavalli A; Lizzi F; Bongarzone S; Brun R; Luise Krauth-Siegel R; Bolognesi ML. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 19:(2009), pp. 3031-3035. [10.1016/j.bmcl.2009.04.060]
Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase
CAVALLI, ANDREA;LIZZI, FEDERICA;BOLOGNESI, MARIA LAURA
2009
Abstract
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 candidatesI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
