WC-9 a lead drug with great prospects for American trypanosomiasis and toxoplasmosis
Trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholest...
Guardado en:
| Autor principal: | |
|---|---|
| Publicado: |
2016
|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13895575_v16_n15_p1195_Rodriguez http://hdl.handle.net/20.500.12110/paper_13895575_v16_n15_p1195_Rodriguez |
| Aporte de: |
| id |
paper:paper_13895575_v16_n15_p1195_Rodriguez |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_13895575_v16_n15_p1195_Rodriguez2023-06-08T16:13:09Z WC-9 a lead drug with great prospects for American trypanosomiasis and toxoplasmosis Rodríguez, Juan Bautista Antiparasitic agents Chagas disease Squalene synthase Toxoplasmosis WC-9 4 phenoxyphenoxyethyl thiocyanate ergosterol squalene synthase thiocyanic acid derivative unclassified drug 4-phenoxyphenoxyethyl thiocyanate antiparasitic agent antitrypanosomal agent diphenyl ether derivative thiocyanic acid derivative cell proliferation Chagas disease enzyme activity enzyme inhibition lipogenesis nonhuman Review structure activity relation Toxoplasma gondii toxoplasmosis Trypanosoma cruzi animal Chagas disease chemistry drug design drug effects human Toxoplasma toxoplasmosis Animals Antiparasitic Agents Chagas Disease Drug Design Humans Phenyl Ethers Thiocyanates Toxoplasma Toxoplasmosis Trypanocidal Agents Trypanosoma cruzi Trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien- 3β-ol brings forth an inhibition of proliferation on Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas disease. These metabolites are crucial; consequently, the enzymes implicated in catalyzing their formation constitute interesting molecular targets for drug design. Selective inhibition of an enzyme associated to the ergosterol biosynthesis will produce T. cruzi cell arrest. Trypanosomatids, fungi, and yeasts have need of these endogenous sterols for cell viability and growth. In fact, some effective ergosterol biosynthesis inhibitors bearing suitable pharmacokinetic properties in mammals have become putative antiparasitic agents by inducing almost complete parasitological cure in both acute and chronic experimental Chagas disease. WC-9 (compound 7; 4-phenoxyphenoxyethyl thiocyanate) holds our attention bearing in mind that this compound exhibits ED50 values at the low nanomolar range against the clinically more relevant replicative form of T. cruzi (amastigotes). The cellular activity of WC-9 is due to an exhaustion of endogenous sterols demonstrating a blockade of the biosynthetic pathway at a pre-squalene level. © 2016 Bentham Science Publishers. Fil:Rodriguez, J.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13895575_v16_n15_p1195_Rodriguez http://hdl.handle.net/20.500.12110/paper_13895575_v16_n15_p1195_Rodriguez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Antiparasitic agents Chagas disease Squalene synthase Toxoplasmosis WC-9 4 phenoxyphenoxyethyl thiocyanate ergosterol squalene synthase thiocyanic acid derivative unclassified drug 4-phenoxyphenoxyethyl thiocyanate antiparasitic agent antitrypanosomal agent diphenyl ether derivative thiocyanic acid derivative cell proliferation Chagas disease enzyme activity enzyme inhibition lipogenesis nonhuman Review structure activity relation Toxoplasma gondii toxoplasmosis Trypanosoma cruzi animal Chagas disease chemistry drug design drug effects human Toxoplasma toxoplasmosis Animals Antiparasitic Agents Chagas Disease Drug Design Humans Phenyl Ethers Thiocyanates Toxoplasma Toxoplasmosis Trypanocidal Agents Trypanosoma cruzi |
| spellingShingle |
Antiparasitic agents Chagas disease Squalene synthase Toxoplasmosis WC-9 4 phenoxyphenoxyethyl thiocyanate ergosterol squalene synthase thiocyanic acid derivative unclassified drug 4-phenoxyphenoxyethyl thiocyanate antiparasitic agent antitrypanosomal agent diphenyl ether derivative thiocyanic acid derivative cell proliferation Chagas disease enzyme activity enzyme inhibition lipogenesis nonhuman Review structure activity relation Toxoplasma gondii toxoplasmosis Trypanosoma cruzi animal Chagas disease chemistry drug design drug effects human Toxoplasma toxoplasmosis Animals Antiparasitic Agents Chagas Disease Drug Design Humans Phenyl Ethers Thiocyanates Toxoplasma Toxoplasmosis Trypanocidal Agents Trypanosoma cruzi Rodríguez, Juan Bautista WC-9 a lead drug with great prospects for American trypanosomiasis and toxoplasmosis |
| topic_facet |
Antiparasitic agents Chagas disease Squalene synthase Toxoplasmosis WC-9 4 phenoxyphenoxyethyl thiocyanate ergosterol squalene synthase thiocyanic acid derivative unclassified drug 4-phenoxyphenoxyethyl thiocyanate antiparasitic agent antitrypanosomal agent diphenyl ether derivative thiocyanic acid derivative cell proliferation Chagas disease enzyme activity enzyme inhibition lipogenesis nonhuman Review structure activity relation Toxoplasma gondii toxoplasmosis Trypanosoma cruzi animal Chagas disease chemistry drug design drug effects human Toxoplasma toxoplasmosis Animals Antiparasitic Agents Chagas Disease Drug Design Humans Phenyl Ethers Thiocyanates Toxoplasma Toxoplasmosis Trypanocidal Agents Trypanosoma cruzi |
| description |
Trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien- 3β-ol brings forth an inhibition of proliferation on Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas disease. These metabolites are crucial; consequently, the enzymes implicated in catalyzing their formation constitute interesting molecular targets for drug design. Selective inhibition of an enzyme associated to the ergosterol biosynthesis will produce T. cruzi cell arrest. Trypanosomatids, fungi, and yeasts have need of these endogenous sterols for cell viability and growth. In fact, some effective ergosterol biosynthesis inhibitors bearing suitable pharmacokinetic properties in mammals have become putative antiparasitic agents by inducing almost complete parasitological cure in both acute and chronic experimental Chagas disease. WC-9 (compound 7; 4-phenoxyphenoxyethyl thiocyanate) holds our attention bearing in mind that this compound exhibits ED50 values at the low nanomolar range against the clinically more relevant replicative form of T. cruzi (amastigotes). The cellular activity of WC-9 is due to an exhaustion of endogenous sterols demonstrating a blockade of the biosynthetic pathway at a pre-squalene level. © 2016 Bentham Science Publishers. |
| author |
Rodríguez, Juan Bautista |
| author_facet |
Rodríguez, Juan Bautista |
| author_sort |
Rodríguez, Juan Bautista |
| title |
WC-9 a lead drug with great prospects for American trypanosomiasis and toxoplasmosis |
| title_short |
WC-9 a lead drug with great prospects for American trypanosomiasis and toxoplasmosis |
| title_full |
WC-9 a lead drug with great prospects for American trypanosomiasis and toxoplasmosis |
| title_fullStr |
WC-9 a lead drug with great prospects for American trypanosomiasis and toxoplasmosis |
| title_full_unstemmed |
WC-9 a lead drug with great prospects for American trypanosomiasis and toxoplasmosis |
| title_sort |
wc-9 a lead drug with great prospects for american trypanosomiasis and toxoplasmosis |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13895575_v16_n15_p1195_Rodriguez http://hdl.handle.net/20.500.12110/paper_13895575_v16_n15_p1195_Rodriguez |
| work_keys_str_mv |
AT rodriguezjuanbautista wc9aleaddrugwithgreatprospectsforamericantrypanosomiasisandtoxoplasmosis |
| _version_ |
1768545524060782592 |