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Abstract:

Chagas disease or American Trypanosomiasis, a parasitic infection typically spread by triatomine bugs, affects millions of people throughout Latin America. Current chemotherapy based on the nitroaromatic compounds, benznidazole and nifurtimox provides unsatisfactory results and suffers from considerable side effects and low efficacy. Therefore, there is an urgent need for new drugs to treat this neglected disease. Over the last two decades, new advances and understanding in the biology and the biochemistry of Trypanosoma cruzi has allowed the identification of multiple targets for Chagas disease chemotherapy. This review summarizes antichagasic agents obtained based on i) target metabolic biochemical pathways or parasite specific enzymes, ii) natural products and its derivatives, iii) design and synthesis of lead compounds. Related patents filed and issued from 2000 to early 2006 are also discussed. Most of them claimed inhibitors on specific parasite targets such as cysteine proteinase, sterol biosynthesis, protein farnesyltransferase, etc. Particularly, those related to cysteine proteinase inhibitors were the most represented. Natural products also displayed many anti-T cruzi lead compounds. In addition, a few patents claiming natural or synthetic compounds with antichagasic activity, disclosed no specific target. However, only a small proportion of all these patents displayed specific data of biological trypanocidal activity. © 2007 Bentham Science Publishers Ltd.

Registro:

Documento: Artículo
Título:An insight on targets and patented drugs for chemotherapy of chagas disease
Autor:Duschak, V.G.; Couto, A.S.
Filiación:Instituto Nacional de Parasitologia Dr. Mario Fatala Chabén, ANLIS-Malbrán, Ministerio de Salud, Av. Paseo Colon 568, 1063 Buenos Aires, Argentina
CIHIDECAR (CONICET), Departamento de Química Orgánica, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Palabras clave:Chagas disease; Drug targets; Natural and synthetic inhibitor compounds; Trypanosoma cruzi; 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; 2 [2 (2,4 difluorophenyl) 2 hydroxy 1 methyl 3 (1h 1,2,4 triazol 1 yl)propyl] 4 [4 (2,2,3,3 tetrafluoropropoxy)phenyl] 1,2,4 triazol 3(2h) one; albaconazole; alendronic acid; amiodarone; amphotericin B lipid complex; aromatic nitro compound; benznidazole; cathepsin K inhibitor; etidronic acid; fluconazole; imidazole derivative; itraconazole; ketoconazole; mevinolin; nifuroxime; nifurtimox; nitrile; pamidronic acid; posaconazole; proteinase inhibitor; pyridinium derivative; quinuclidine derivative; ravuconazole; risedronic acid; terbinafine; thiocyanic acid derivative; thiosemicarbazone derivative; tipifarnib; unindexed drug; biochemistry; Chagas disease; clinical trial; drug design; drug efficacy; drug potentiation; drug structure; drug synthesis; drug targeting; human; leishmaniasis; malaria; nonhuman; osteoporosis; patent; priority journal; review; sterol synthesis; Trypanosoma cruzi; trypanosomiasis; Animals; Arginine Kinase; Biological Products; Chagas Disease; Enzyme Inhibitors; Ergosterol; Glycolysis; Humans; Lipids; Organelles; Patents as Topic; Pentose Phosphate Pathway; Protease Inhibitors; Purines; Sialic Acids; Sulfhydryl Compounds; Terpenes; Trypanocidal Agents; Trypanosoma cruzi
Año:2007
Volumen:2
Número:1
Página de inicio:19
Página de fin:51
DOI: http://dx.doi.org/10.2174/157489107779561625
Título revista:Recent Patents on Anti-Infective Drug Discovery
Título revista abreviado:Recent Pat. Anti-Infect. Drug Discov.
ISSN:1574891X
CAS: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, 103961-78-0, 141113-28-2; 2 [2 (2,4 difluorophenyl) 2 hydroxy 1 methyl 3 (1h 1,2,4 triazol 1 yl)propyl] 4 [4 (2,2,3,3 tetrafluoropropoxy)phenyl] 1,2,4 triazol 3(2h) one, 155432-64-7; albaconazole, 187949-02-6; alendronic acid, 66376-36-1; amiodarone, 1951-25-3, 19774-82-4, 62067-87-2; benznidazole, 22994-85-0; etidronic acid, 2809-21-4, 3794-83-0, 58449-82-4, 7414-83-7; fluconazole, 86386-73-4; itraconazole, 84625-61-6; ketoconazole, 65277-42-1; mevinolin, 75330-75-5; nifuroxime, 555-15-7, 6236-05-1; nifurtimox, 23256-30-6; pamidronic acid, 40391-99-9, 57248-88-1; posaconazole, 171228-49-2; proteinase inhibitor, 37205-61-1; ravuconazole, 182760-06-1; risedronic acid, 105462-24-6, 122458-82-6; terbinafine, 91161-71-6; tipifarnib, 192185-72-1; Arginine Kinase, EC 2.7.3.3; Biological Products; Enzyme Inhibitors; Ergosterol, 57-87-4; Lipids; Protease Inhibitors; Purines; Sialic Acids; Sulfhydryl Compounds; Terpenes; Trypanocidal Agents
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1574891X_v2_n1_p19_Duschak

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Citas:

---------- APA ----------
Duschak, V.G. & Couto, A.S. (2007) . An insight on targets and patented drugs for chemotherapy of chagas disease. Recent Patents on Anti-Infective Drug Discovery, 2(1), 19-51.
http://dx.doi.org/10.2174/157489107779561625
---------- CHICAGO ----------
Duschak, V.G., Couto, A.S. "An insight on targets and patented drugs for chemotherapy of chagas disease" . Recent Patents on Anti-Infective Drug Discovery 2, no. 1 (2007) : 19-51.
http://dx.doi.org/10.2174/157489107779561625
---------- MLA ----------
Duschak, V.G., Couto, A.S. "An insight on targets and patented drugs for chemotherapy of chagas disease" . Recent Patents on Anti-Infective Drug Discovery, vol. 2, no. 1, 2007, pp. 19-51.
http://dx.doi.org/10.2174/157489107779561625
---------- VANCOUVER ----------
Duschak, V.G., Couto, A.S. An insight on targets and patented drugs for chemotherapy of chagas disease. Recent Pat. Anti-Infect. Drug Discov. 2007;2(1):19-51.
http://dx.doi.org/10.2174/157489107779561625