Progresses in the field of drug design to combat tropical protozoan parasitic diseases

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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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Autor principal: García Liñares, G.E
Otros Autores: Ravaschino, E.L, Rodriguez, J.B
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2006
Materias:
AFRICAN TRYPANOSOMIASIS
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100 1 |a García Liñares, G.E. 
245 1 0 |a Progresses in the field of drug design to combat tropical protozoan parasitic diseases 
260 |c 2006 
270 1 0 |m Rodriguez, J.B.; Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, C1428EHA Buenos Aires, Argentina; email: JBR@qo.fcen.uba.ar 
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520 3 |a 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.  |l eng 
593 |a Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, C1428EHA Buenos Aires, Argentina 
690 1 0 |a 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 
690 1 0 |a AMPHOTERICIN B 
690 1 0 |a ANTIPROTOZOAL AGENT 
690 1 0 |a BENZNIDAZOLE 
690 1 0 |a CRYSTAL VIOLET 
690 1 0 |a DIHYDROFOLATE REDUCTASE 
690 1 0 |a DIMETHYLALLYLTRANSFERASE 
690 1 0 |a EFLORNITHINE 
690 1 0 |a ERGOSTEROL 
690 1 0 |a GERANYLTRANSFERASE 
690 1 0 |a GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE 
690 1 0 |a ICI 195 739 
690 1 0 |a KETOCONAZOLE 
690 1 0 |a MEGLUMINE ANTIMONATE 
690 1 0 |a MELARSOPROL 
690 1 0 |a MILTEFOSINE 
690 1 0 |a NIFURTIMOX 
690 1 0 |a ORNITHINE DECARBOXYLASE 
690 1 0 |a PAROMOMYCIN 
690 1 0 |a PENTAMIDINE 
690 1 0 |a SITAMAQUINE 
690 1 0 |a SPERMIDINE DERIVATIVE 
690 1 0 |a SQUALENE SYNTHASE 
690 1 0 |a SURAMIN 
690 1 0 |a TERBINAFINE 
690 1 0 |a THIOCYANIC ACID DERIVATIVE 
690 1 0 |a TRIAZOLE DERIVATIVE 
690 1 0 |a TRYPANOTHIONE 
690 1 0 |a TRYPANOTHIONE REDUCTASE 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a UNINDEXED DRUG 
690 1 0 |a ANTIPROTOZOAL AGENT 
690 1 0 |a ANOREXIA 
690 1 0 |a ANTIBIOTIC SENSITIVITY 
690 1 0 |a ANTIPROTOZOAL ACTIVITY 
690 1 0 |a BIOSYNTHESIS 
690 1 0 |a CHAGAS DISEASE 
690 1 0 |a DISEASE COURSE 
690 1 0 |a DISEASE SEVERITY 
690 1 0 |a DISEASE TRANSMISSION 
690 1 0 |a DRUG DESIGN 
690 1 0 |a DRUG MECHANISM 
690 1 0 |a DRUG RESEARCH 
690 1 0 |a DRUG SPECIFICITY 
690 1 0 |a DRUG STRUCTURE 
690 1 0 |a DRUG TARGETING 
690 1 0 |a GENE TARGETING 
690 1 0 |a HUMAN 
690 1 0 |a INFECTION CONTROL 
690 1 0 |a LEISHMANIASIS 
690 1 0 |a LONG TERM CARE 
690 1 0 |a NONHUMAN 
690 1 0 |a PARASITE SURVIVAL 
690 1 0 |a PERIPHERAL NEUROPATHY 
690 1 0 |a REVIEW 
690 1 0 |a SKIN ALLERGY 
690 1 0 |a STRUCTURE ANALYSIS 
690 1 0 |a TERATOGENICITY 
690 1 0 |a TOXOPLASMA GONDII 
690 1 0 |a TRYPANOSOMA BRUCEI 
690 1 0 |a TRYPANOSOMA CRUZI 
690 1 0 |a VOMITING 
690 1 0 |a CHAGAS DISEASE 
690 1 0 |a DRUG DESIGN 
690 1 0 |a LEISHMANIASIS 
690 1 0 |a TRYPANOSOMIASIS 
690 1 0 |a ANTIPROTOZOAL AGENTS 
690 1 0 |a CHAGAS DISEASE 
690 1 0 |a DRUG DESIGN 
690 1 0 |a HUMANS 
690 1 0 |a LEISHMANIASIS 
690 1 0 |a TRYPANOSOMIASIS 
651 4 |a AFRICAN TRYPANOSOMIASIS 
653 0 0 |a d 0870; ici 195 739 
700 1 |a Ravaschino, E.L. 
700 1 |a Rodriguez, J.B. 
773 0 |d 2006  |g v. 13  |h pp. 335-360  |k n. 3  |p Curr. Med. Chem.  |x 09298673  |t Current Medicinal Chemistry 
856 4 1 |u https://www.scopus.com/inward/record.uri?eid=2-s2.0-33645883558&doi=10.2174%2f092986706775476043&partnerID=40&md5=b8acb95d06cf9771ba5edcaa8c87923b  |y Registro en Scopus 
856 4 0 |u https://doi.org/10.2174/092986706775476043  |y DOI 
856 4 0 |u https://hdl.handle.net/20.500.12110/paper_09298673_v13_n3_p335_GarciaLinares  |y Handle 
856 4 0 |u https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v13_n3_p335_GarciaLinares  |y Registro en la Biblioteca Digital 
961 |a paper_09298673_v13_n3_p335_GarciaLinares  |b paper  |c PE 
962 |a info:eu-repo/semantics/article  |a info:ar-repo/semantics/artículo  |b info:eu-repo/semantics/publishedVersion 
999 |c 68279 

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