Improved Tricyclic Inhibitors of Trypanothione Reductase by Screening and Chemical Synthesis
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چکیده
منابع مشابه
Improved Tricyclic Inhibitors of Trypanothione Reductase by Screening and Chemical Synthesis
Trypanothione reductase (TryR) is a key validated enzyme in the trypanothione-based redox metabolism of pathogenic trypanosomes and leishmania parasites. This system is absent in humans, being replaced with glutathione and glutathione reductase, and as such offers a target for selective inhibition. As part of a program to discover antiparasitic drugs, the LOPAC1280 library of 1266 compounds was...
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The search for novel compounds of relevance to the treatment of diseases caused by trypanosomatid protozoan parasites continues. Screening of a large library of known bioactive compounds has led to several drug-like starting points for further optimisation. In this study, novel analogues of the monoamine uptake inhibitor indatraline were prepared and assessed both as inhibitors of trypanothione...
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Trypanosoma brucei, the causative agent of African sleeping sickness, synthesizes deoxyribonucleotides via a classical eukaryotic class I ribonucleotide reductase. The unique thiol metabolism of trypanosomatids in which the nearly ubiquitous glutathione reductase is replaced by a trypanothione reductase prompted us to study the nature of thiols providing reducing equivalents for the parasite sy...
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An improved multistep synthesis of tricyclic α-cyanopyrrolidine from camphor is presented. The synthesis was carried out by maintaining the cyano group in the form of an amide and its regeneration after the completion of the necessary chemical transformation of a particular functional group. The tricyclic α-cyanopyrrolidine prepared was used to synthesize two novel compounds of DPP4 (Dipeptidyl...
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High-throughput screening of 100,000 lead-like compounds led to the identification of nine novel chemical classes of trypanothione reductase (TR) inhibitors worthy of further investigation. Hits from five of these chemical classes have been developed further through different combinations of preliminary structure-activity relationship rate probing and assessment of antiparasitic activity, cytot...
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ژورنال
عنوان ژورنال: ChemMedChem
سال: 2009
ISSN: 1860-7179
DOI: 10.1002/cmdc.200900097