Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase

Andrea Cavalli; Federica Lizzi; Salvatore Bongarzone; Reto Brun; R Luise Krauth-Siegel; Maria Laura Bolognesi

doi:10.1016/j.bmcl.2009.04.060

Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase

Andrea Cavalli, Federica Lizzi, Salvatore Bongarzone, Reto Brun, R Luise Krauth-Siegel, Maria Laura Bolognesi

Imaging Chemistry & Biology

University of Bologna

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

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 candidates.

Original language	English
Pages (from-to)	3031-5
Number of pages	5
Journal	Bioorganic & medicinal chemistry letters
Volume	19
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2009.04.060
Publication status	Published - 1 Jun 2009

Keywords

Animals
Antiparasitic Agents/chemical synthesis
Cell Line
Computer Simulation
Drug Design
Enzyme Inhibitors/chemical synthesis
Glutathione Reductase/antagonists & inhibitors
Humans
NADH, NADPH Oxidoreductases/antagonists & inhibitors
Quinazolines/chemical synthesis
Rats
Structure-Activity Relationship
Trypanosoma cruzi/drug effects

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2009.04.060

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title = "Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase",

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 candidates.",

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author = "Andrea Cavalli and Federica Lizzi and Salvatore Bongarzone and Reto Brun and {Luise Krauth-Siegel}, R and Bolognesi, {Maria Laura}",

year = "2009",

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doi = "10.1016/j.bmcl.2009.04.060",

language = "English",

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journal = "Bioorganic & medicinal chemistry letters",

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TY - JOUR

T1 - Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase

AU - Cavalli, Andrea

AU - Lizzi, Federica

AU - Bongarzone, Salvatore

AU - Brun, Reto

AU - Luise Krauth-Siegel, R

AU - Bolognesi, Maria Laura

PY - 2009/6/1

Y1 - 2009/6/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antiparasitic Agents/chemical synthesis

KW - Cell Line

KW - Computer Simulation

KW - Drug Design

KW - Enzyme Inhibitors/chemical synthesis

KW - Glutathione Reductase/antagonists & inhibitors

KW - Humans

KW - NADH, NADPH Oxidoreductases/antagonists & inhibitors

KW - Quinazolines/chemical synthesis

KW - Rats

KW - Structure-Activity Relationship

KW - Trypanosoma cruzi/drug effects

U2 - 10.1016/j.bmcl.2009.04.060

DO - 10.1016/j.bmcl.2009.04.060

M3 - Article

C2 - 19414258

SN - 0960-894X

VL - 19

SP - 3031

EP - 3035

JO - Bioorganic & medicinal chemistry letters

JF - Bioorganic & medicinal chemistry letters

IS - 11

ER -

Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase

Abstract

Keywords

UN SDGs

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