Progresses in the field of drug design to combat tropical protozoan parasitic diseases
The progresses made in the field of drug design to combat tropical protozoan parasitic diseases, such as Chagas' disease, leishmaniasis, and sleeping sickness are discussed. This article is focused on different approaches based on unique aspects of parasites biochemistry and physiology, selecti...
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| Publicado: |
2006
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v13_n3_p335_GarciaLinares http://hdl.handle.net/20.500.12110/paper_09298673_v13_n3_p335_GarciaLinares |
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paper:paper_09298673_v13_n3_p335_GarciaLinares |
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dspace |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
2 (2,4 difluorophenyl) 1 [3 [2 [4 (2,2,3,3 tetrafluoropropoxy)phenyl]vinyl] 1,2,4 triazol 1 yl] 3 (1,2,4 triazol 1 yl) 2 propanol amphotericin B antiprotozoal agent benznidazole crystal violet dihydrofolate reductase dimethylallyltransferase eflornithine ergosterol geranyltransferase glyceraldehyde 3 phosphate dehydrogenase ici 195 739 ketoconazole meglumine antimonate melarsoprol miltefosine nifurtimox ornithine decarboxylase paromomycin pentamidine sitamaquine spermidine derivative squalene synthase suramin terbinafine thiocyanic acid derivative triazole derivative trypanothione trypanothione reductase unclassified drug unindexed drug antiprotozoal agent African trypanosomiasis anorexia antibiotic sensitivity antiprotozoal activity biosynthesis Chagas disease disease course disease severity disease transmission drug design drug mechanism drug research drug specificity drug structure drug targeting gene targeting human infection control leishmaniasis long term care nonhuman parasite survival peripheral neuropathy review skin allergy structure analysis teratogenicity Toxoplasma gondii Trypanosoma brucei Trypanosoma cruzi vomiting Chagas disease drug design leishmaniasis trypanosomiasis Antiprotozoal Agents Chagas Disease Drug Design Humans Leishmaniasis Trypanosomiasis |
| spellingShingle |
2 (2,4 difluorophenyl) 1 [3 [2 [4 (2,2,3,3 tetrafluoropropoxy)phenyl]vinyl] 1,2,4 triazol 1 yl] 3 (1,2,4 triazol 1 yl) 2 propanol amphotericin B antiprotozoal agent benznidazole crystal violet dihydrofolate reductase dimethylallyltransferase eflornithine ergosterol geranyltransferase glyceraldehyde 3 phosphate dehydrogenase ici 195 739 ketoconazole meglumine antimonate melarsoprol miltefosine nifurtimox ornithine decarboxylase paromomycin pentamidine sitamaquine spermidine derivative squalene synthase suramin terbinafine thiocyanic acid derivative triazole derivative trypanothione trypanothione reductase unclassified drug unindexed drug antiprotozoal agent African trypanosomiasis anorexia antibiotic sensitivity antiprotozoal activity biosynthesis Chagas disease disease course disease severity disease transmission drug design drug mechanism drug research drug specificity drug structure drug targeting gene targeting human infection control leishmaniasis long term care nonhuman parasite survival peripheral neuropathy review skin allergy structure analysis teratogenicity Toxoplasma gondii Trypanosoma brucei Trypanosoma cruzi vomiting Chagas disease drug design leishmaniasis trypanosomiasis Antiprotozoal Agents Chagas Disease Drug Design Humans Leishmaniasis Trypanosomiasis García Liñares, Guadalupe E. Ravaschino, Esteban Luis Rodríguez, Juan Bautista Progresses in the field of drug design to combat tropical protozoan parasitic diseases |
| topic_facet |
2 (2,4 difluorophenyl) 1 [3 [2 [4 (2,2,3,3 tetrafluoropropoxy)phenyl]vinyl] 1,2,4 triazol 1 yl] 3 (1,2,4 triazol 1 yl) 2 propanol amphotericin B antiprotozoal agent benznidazole crystal violet dihydrofolate reductase dimethylallyltransferase eflornithine ergosterol geranyltransferase glyceraldehyde 3 phosphate dehydrogenase ici 195 739 ketoconazole meglumine antimonate melarsoprol miltefosine nifurtimox ornithine decarboxylase paromomycin pentamidine sitamaquine spermidine derivative squalene synthase suramin terbinafine thiocyanic acid derivative triazole derivative trypanothione trypanothione reductase unclassified drug unindexed drug antiprotozoal agent African trypanosomiasis anorexia antibiotic sensitivity antiprotozoal activity biosynthesis Chagas disease disease course disease severity disease transmission drug design drug mechanism drug research drug specificity drug structure drug targeting gene targeting human infection control leishmaniasis long term care nonhuman parasite survival peripheral neuropathy review skin allergy structure analysis teratogenicity Toxoplasma gondii Trypanosoma brucei Trypanosoma cruzi vomiting Chagas disease drug design leishmaniasis trypanosomiasis Antiprotozoal Agents Chagas Disease Drug Design Humans Leishmaniasis Trypanosomiasis |
| description |
The progresses made in the field of drug design to combat tropical protozoan parasitic diseases, such as Chagas' disease, leishmaniasis, and sleeping sickness are discussed. This article is focused on different approaches based on unique aspects of parasites biochemistry and physiology, selecting the more promising molecular targets for drug design. In spite of the enormous amount of work on the above features, the chemotherapy for all of these diseases remains unsolved. It is based on old and fairly not specific drugs associated, in several cases, with long-term treatments and severe side effects. Drug resistance and different strains susceptibility are further drawbacks of the existing chemotherapy. In this review article, a thorough analysis of selected molecular targets, mainly those that are significantly different compared with the mammalian host or, even, are not present in mammals would be described in terms of their potencial usefulness for drug design. Therefore, this article covers rational approaches to the chemotherapeutic control of these parasitic infections, such as the progresses in the search for novel metabolic pathways in parasites that may be essential for parasites survival but with no counterpart in the host. Ergosterol biosynthesis is a very interesting example. There are many enzymes involved in this biosynthetic pathway such us squalene synthase, farnesylpyrophosphate synthase, and other enzymes that are able to deplete endogenous sterols will be treated in this article. The enzymes involved in trypanothione biosynthesis, glutathionyl spermidine synthetase and trypanothione synthetase do not have an equivalent in mammals, and therefore it can be predicted low toxicity for compounds that are able to produce highly selective inhibition. Trypanothione reductase (TR), glyceraldehyde-3-phosphate dehydrogenase, dihydrofolate reductase, prenyltransferases, ornithine decarboxylase, etc, will be thoroughly analyzed. The design of specific inhibitors of such metabolic activities as possible means of controlling the parasites without damaging the hosts will be presented. The recent advances in the biochemistry of pathogenic parasites including the discovery of novel organelles will be discussed. © 2006 Bentham Science Publishers Ltd. |
| author |
García Liñares, Guadalupe E. Ravaschino, Esteban Luis Rodríguez, Juan Bautista |
| author_facet |
García Liñares, Guadalupe E. Ravaschino, Esteban Luis Rodríguez, Juan Bautista |
| author_sort |
García Liñares, Guadalupe E. |
| title |
Progresses in the field of drug design to combat tropical protozoan parasitic diseases |
| title_short |
Progresses in the field of drug design to combat tropical protozoan parasitic diseases |
| title_full |
Progresses in the field of drug design to combat tropical protozoan parasitic diseases |
| title_fullStr |
Progresses in the field of drug design to combat tropical protozoan parasitic diseases |
| title_full_unstemmed |
Progresses in the field of drug design to combat tropical protozoan parasitic diseases |
| title_sort |
progresses in the field of drug design to combat tropical protozoan parasitic diseases |
| publishDate |
2006 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v13_n3_p335_GarciaLinares http://hdl.handle.net/20.500.12110/paper_09298673_v13_n3_p335_GarciaLinares |
| work_keys_str_mv |
AT garcialinaresguadalupee progressesinthefieldofdrugdesigntocombattropicalprotozoanparasiticdiseases AT ravaschinoestebanluis progressesinthefieldofdrugdesigntocombattropicalprotozoanparasiticdiseases AT rodriguezjuanbautista progressesinthefieldofdrugdesigntocombattropicalprotozoanparasiticdiseases |
| _version_ |
1768546759019069440 |
| spelling |
paper:paper_09298673_v13_n3_p335_GarciaLinares2023-06-08T15:52:26Z Progresses in the field of drug design to combat tropical protozoan parasitic diseases García Liñares, Guadalupe E. Ravaschino, Esteban Luis Rodríguez, Juan Bautista 2 (2,4 difluorophenyl) 1 [3 [2 [4 (2,2,3,3 tetrafluoropropoxy)phenyl]vinyl] 1,2,4 triazol 1 yl] 3 (1,2,4 triazol 1 yl) 2 propanol amphotericin B antiprotozoal agent benznidazole crystal violet dihydrofolate reductase dimethylallyltransferase eflornithine ergosterol geranyltransferase glyceraldehyde 3 phosphate dehydrogenase ici 195 739 ketoconazole meglumine antimonate melarsoprol miltefosine nifurtimox ornithine decarboxylase paromomycin pentamidine sitamaquine spermidine derivative squalene synthase suramin terbinafine thiocyanic acid derivative triazole derivative trypanothione trypanothione reductase unclassified drug unindexed drug antiprotozoal agent African trypanosomiasis anorexia antibiotic sensitivity antiprotozoal activity biosynthesis Chagas disease disease course disease severity disease transmission drug design drug mechanism drug research drug specificity drug structure drug targeting gene targeting human infection control leishmaniasis long term care nonhuman parasite survival peripheral neuropathy review skin allergy structure analysis teratogenicity Toxoplasma gondii Trypanosoma brucei Trypanosoma cruzi vomiting Chagas disease drug design leishmaniasis trypanosomiasis Antiprotozoal Agents Chagas Disease Drug Design Humans Leishmaniasis Trypanosomiasis The progresses made in the field of drug design to combat tropical protozoan parasitic diseases, such as Chagas' disease, leishmaniasis, and sleeping sickness are discussed. This article is focused on different approaches based on unique aspects of parasites biochemistry and physiology, selecting the more promising molecular targets for drug design. In spite of the enormous amount of work on the above features, the chemotherapy for all of these diseases remains unsolved. It is based on old and fairly not specific drugs associated, in several cases, with long-term treatments and severe side effects. Drug resistance and different strains susceptibility are further drawbacks of the existing chemotherapy. In this review article, a thorough analysis of selected molecular targets, mainly those that are significantly different compared with the mammalian host or, even, are not present in mammals would be described in terms of their potencial usefulness for drug design. Therefore, this article covers rational approaches to the chemotherapeutic control of these parasitic infections, such as the progresses in the search for novel metabolic pathways in parasites that may be essential for parasites survival but with no counterpart in the host. Ergosterol biosynthesis is a very interesting example. There are many enzymes involved in this biosynthetic pathway such us squalene synthase, farnesylpyrophosphate synthase, and other enzymes that are able to deplete endogenous sterols will be treated in this article. The enzymes involved in trypanothione biosynthesis, glutathionyl spermidine synthetase and trypanothione synthetase do not have an equivalent in mammals, and therefore it can be predicted low toxicity for compounds that are able to produce highly selective inhibition. Trypanothione reductase (TR), glyceraldehyde-3-phosphate dehydrogenase, dihydrofolate reductase, prenyltransferases, ornithine decarboxylase, etc, will be thoroughly analyzed. The design of specific inhibitors of such metabolic activities as possible means of controlling the parasites without damaging the hosts will be presented. The recent advances in the biochemistry of pathogenic parasites including the discovery of novel organelles will be discussed. © 2006 Bentham Science Publishers Ltd. Fil:García Liñares, G.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ravaschino, E.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rodriguez, J.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v13_n3_p335_GarciaLinares http://hdl.handle.net/20.500.12110/paper_09298673_v13_n3_p335_GarciaLinares |