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Medicina (Buenos Aires)
versión impresa ISSN 0025-7680versión On-line ISSN 1669-9106
Resumen
REGUERA, Rosa M et al. Type I DNA topoisomerase from protozoan pathogens as a potential target for anti-tumoral drugs. Medicina (B. Aires) [online]. 2007, vol.67, n.6, pp.747-757. ISSN 0025-7680.
The intensive use of antiparasitic drugs is the main cause of the emergence of multiresistant parasite strains on those regions where these parasites are endemic. The aetiological agents of the so-called tropical diseases viz. malaria, cryptosporidiosis, sleeping sickness, Chagas disease or leishmaniasis, among others, are unicellular protozoan parasites with no immune-prophylactic treatment and where the chemotherapeutical treatment is still under controversy. At present, the chemotherapeutic approach to these diseases is expensive, has side or toxic effects and it does not provide economic profits to the Pharmaceuticals which then have no or scarce enthusiasm in R & D investments in this field. The identification of type I DNAtopoisomerases as promising drug targets is based on the excellent results obtained with camptothecin derivatives in anticancer therapy. The recent finding of significant structural differences between human type I DNAtopoisomerase and their counterparts in trypanosomatids has open a new field in drug discovery, the aim is to find structural insights to be targeted by new drugs. This review is an update of DNA-topoisomerases as potential chemotherapeutic targets against the most important protozoan agents of medical interest.
Palabras clave : DNA topology; Type I DNA topoisomerase; Camptothecin; Tropical diseases.