Macromolecular Bases of Antischistosomal Therapy

Author(s): Francesco Angelucci, Adriana Erica Miele, Giovanna Boumis, Maurizio Brunori, Daniela Dimastrogiovanni, Andrea Bellelli.

Journal Name: Current Topics in Medicinal Chemistry

Volume 11 , Issue 16 , 2011

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Abstract:

Schistosomiasis is a widespread tropical parasitic disease, currently treated with Praziquantel, whose precise molecular target is actually unknown. Several other drugs are known to kill the schistosomes in vivo and in vitro, but these are seldom employed because of toxicity, high cost, complex administration or other reasons. The improvement of known drugs or the development of entirely new ones is a desirable goal, in view of the fact that strains of Schistosoma mansoni with reduced sensitivity to Praziquantel have appeared. In this review, we tried to collect the information available on known or putative macromolecular targets of schistosomicidal drugs; thus we focused on the biochemistry of the parasite, rather than the clinical properties of the drugs. The rationale of this approach is that drug design may become realistic if the mechanism of action of each known drug were known at atomic detail, ideally as the 3D structure of each drug in complex with its target. Important macromolecular targets of known drugs reviewed below are: Thioredoxin Glutathione Reductase; Cyclophilin; Acetyl Cholinesterase; Proteases and Purine Nucleoside Phosphorylase. Moreover, a few enzymes of the parasite are known, or thought, to be “druggable”, and therefore interesting, even though no specific drugs are available as yet: examples of such enzymes are Glutathione Peroxidase and Peroxiredoxins.

Keywords: Artemisinin, auranofin, neglected tropical disease, oxamniquine, praziquantel, proteases, thioredoxin glutathione reductase, Schistosomiasis, crystal structure, schistosomes, toxicity, Cyclophilin, Acetyl Cholinesterase, druggable

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Article Details

VOLUME: 11
ISSUE: 16
Year: 2011
Page: [2012 - 2028]
Pages: 17
DOI: 10.2174/156802611796575939
Price: $58

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