DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery
11 páginas, 1 figura.
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Royal Society (Great Britain)
2010
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| Subjects: | Apicomplexan protozoa, Chemotherapy, DNA topoisomerases, Tropical diseases, |
| Online Access: | http://hdl.handle.net/10261/104738 |
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dig-igm-es-10261-1047382022-06-03T09:37:30Z DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery García-Estrada, Carlos Prada, C. F. Fernández-Rubio, Celia Rojo Vázquez, Francisco Antonio Balaña-Fouce, Rafael Apicomplexan protozoa Chemotherapy DNA topoisomerases Tropical diseases 11 páginas, 1 figura. The phylum Apicomplexa includes a large group of protozoan parasites responsible for a wide range of animal and human diseases. Destructive pathogens, such as Plasmodium falciparum and Plasmodium vivax, causative agents of human malaria, Cryptosporidium parvum, responsible of childhood diarrhoea, and Toxoplasma gondii, responsible for miscarriages and abortions in humans, are frequently associated with HIV immunosuppression in AIDS patients. The lack of effective vaccines, along with years of increasing pressure to eradicate outbreaks with the use of drugs, has favoured the formation of multi-drug resistant strains in endemic areas. Almost all apicomplexan of medical interest contain two endosymbiotic organelles that contain their own mitochondrial and apicoplast DNA. Apicoplast is an attractive target for drug testing because in addition to harbouring singular metabolic pathways absent in the host, it also has its own transcription and translation machinery of bacterial origin. Accordingly, apicomplexan protozoa contain an interesting mixture of enzymes to unwind DNA from eukaryotic and prokaryotic origins. On the one hand, the main mechanism of DNA unwinding includes the scission of one-type I-or both DNA strands-type II eukaryotic topoisomerases, establishing transient covalent bonds with the scissile end. These enzymes are targeted by camptothecin and etoposide, respectively, two natural drugs whose semisynthetic derivatives are currently used in cancer chemotherapy. On the other hand, DNA gyrase is a bacterial-borne type II DNA topoisomerase that operates within the apicoplast and is effectively targeted by bacterial antibiotics like fluoroquinolones and aminocoumarins. The present review is an update on the new findings concerning topoisomerases in apicomplexan parasites and the role of these enzymes as targets for therapeutic This research was supported by Ministerio de Ciencia e Innovation (grants AGL2003 06976/GAN and AGL2006-07420/GAN), Gr-238 from Junta de Castilla y León and the Tropical Diseases Network (RICET) from Ministerio de Salud y Consumo from the Spanish Kingdom. Peer Reviewed 2014-11-10T12:20:13Z 2014-11-10T12:20:13Z 2010 2014-11-10T12:20:13Z artículo http://purl.org/coar/resource_type/c_6501 Proceedings of the Royal Society B: Biological Sciences 277: 1777-1787 (2010) 0962-8452 http://hdl.handle.net/10261/104738 10.1098/rspb.2009.2176 20200034 http://dx.doi.org/10.1098/rspb.2009.2176 none Royal Society (Great Britain) |
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Apicomplexan protozoa Chemotherapy DNA topoisomerases Tropical diseases Apicomplexan protozoa Chemotherapy DNA topoisomerases Tropical diseases |
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Apicomplexan protozoa Chemotherapy DNA topoisomerases Tropical diseases Apicomplexan protozoa Chemotherapy DNA topoisomerases Tropical diseases García-Estrada, Carlos Prada, C. F. Fernández-Rubio, Celia Rojo Vázquez, Francisco Antonio Balaña-Fouce, Rafael DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery |
| description |
11 páginas, 1 figura. |
| format |
artículo |
| topic_facet |
Apicomplexan protozoa Chemotherapy DNA topoisomerases Tropical diseases |
| author |
García-Estrada, Carlos Prada, C. F. Fernández-Rubio, Celia Rojo Vázquez, Francisco Antonio Balaña-Fouce, Rafael |
| author_facet |
García-Estrada, Carlos Prada, C. F. Fernández-Rubio, Celia Rojo Vázquez, Francisco Antonio Balaña-Fouce, Rafael |
| author_sort |
García-Estrada, Carlos |
| title |
DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery |
| title_short |
DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery |
| title_full |
DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery |
| title_fullStr |
DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery |
| title_full_unstemmed |
DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery |
| title_sort |
dna topoisomerases in apicomplexan parasites: promising targets for drug discovery |
| publisher |
Royal Society (Great Britain) |
| publishDate |
2010 |
| url |
http://hdl.handle.net/10261/104738 |
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