Artículo

Elicio, P.D.; Chao, M.N.; Galizzi, M.; Li, C.; Szajnman, S.H.; Docampo, R.; Moreno, S.N.J.; Rodriguez, J.B. "Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents" (2013) European Journal of Medicinal Chemistry. 69:480-489
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Abstract:

As a part of our project pointed at the search of new safe chemotherapeutic and chemoprophylactic agents against parasitic diseases, several compounds structurally related to 4-phenoxyphenoxyethyl thiocyanate (WC-9), which were modified at the terminal aromatic ring, were designed, synthesized and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible of American trypanosomiasis (Chagas disease) and Toxoplasma gondii, the etiological agent of toxoplasmosis. Most of the synthetic analogs exhibited similar antiparasitic activity being slightly more potent than the reference compound WC-9. For example, the nitro derivative 13 showed an ED50 value of 5.2 μM. Interestingly, the regioisomer of WC-9, compound 36 showed similar inhibitory action than WC-9 indicating that para-phenyl substitution pattern is not necessarily required for biological activity. The biological evaluation against T. gondii was also very promising. The ED50 values corresponding for 13, 36 and 37 were at the very low micromolar level against tachyzoites of T. gondii. © 2013 Elsevier Masson SAS. All rights reserved.

Registro:

Documento: Artículo
Título:Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents
Autor:Elicio, P.D.; Chao, M.N.; Galizzi, M.; Li, C.; Szajnman, S.H.; Docampo, R.; Moreno, S.N.J.; Rodriguez, J.B.
Filiación:Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, C1428EHA Buenos Aires, Argentina
Center for Tropical and Emerging Global Diseases, Department of Cellular Biology, University of Georgia, Athens, GA 30602, United States
Palabras clave:Antiparasitic agents; Chagas disease; Squalene synthase inhibitors; Toxoplasma gondii WC-9 analogs; Toxoplasmosis; Trypanosoma cruzi; 3 (4 methoxyphenoxy)phenoxyethyl thiocyanate; 3 phenoxyphenoxyethyl thiocyanate; 4 (3 methoxyphenoxy)phenoxyethyl thiocyanate; 4 (3 nitrophenoxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether; 4 (3 nitrophenoxy)phenoxyethyl thiocyanate; 4 (4 methoxyphenoxy)phenoxyethyl thiocyanate; 4 (pyridin 3 yloxy)phenoxyethyl tetrahydro 2h pyran 2 yl ether; 4 (pyridin 3 yloxy)phenoxyethyl thiocyanate; 4 phenoxyphenoxyethyl thiocyanate; antiparasitic agent; atovaquone; benznidazole; nitro derivative; thiocyanic acid derivative; unclassified drug; antiproliferative activity; article; biological activity; Chagas disease; controlled study; drug cytotoxicity; drug design; drug screening; drug synthesis; nonhuman; tachyzoite; Toxoplasma gondii; toxoplasmosis; Trypanosoma cruzi; Antiparasitic agents; Chagas disease; Squalene synthase inhibitors; Toxoplasma gondii; Toxoplasmosis; Trypanosoma cruzi; WC-9 analogs; Antiparasitic Agents; Dose-Response Relationship, Drug; Drug Design; Molecular Structure; Parasitic Sensitivity Tests; Phenyl Ethers; Structure-Activity Relationship; Thiocyanates; Toxoplasma; Trypanosoma cruzi
Año:2013
Volumen:69
Página de inicio:480
Página de fin:489
DOI: http://dx.doi.org/10.1016/j.ejmech.2013.09.009
Título revista:European Journal of Medicinal Chemistry
Título revista abreviado:Eur. J. Med. Chem.
ISSN:02235234
CODEN:EJMCA
CAS:atovaquone, 94015-53-9, 95233-18-4; benznidazole, 22994-85-0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v69_n_p480_Elicio

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Citas:

---------- APA ----------
Elicio, P.D., Chao, M.N., Galizzi, M., Li, C., Szajnman, S.H., Docampo, R., Moreno, S.N.J.,..., Rodriguez, J.B. (2013) . Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents. European Journal of Medicinal Chemistry, 69, 480-489.
http://dx.doi.org/10.1016/j.ejmech.2013.09.009
---------- CHICAGO ----------
Elicio, P.D., Chao, M.N., Galizzi, M., Li, C., Szajnman, S.H., Docampo, R., et al. "Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents" . European Journal of Medicinal Chemistry 69 (2013) : 480-489.
http://dx.doi.org/10.1016/j.ejmech.2013.09.009
---------- MLA ----------
Elicio, P.D., Chao, M.N., Galizzi, M., Li, C., Szajnman, S.H., Docampo, R., et al. "Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents" . European Journal of Medicinal Chemistry, vol. 69, 2013, pp. 480-489.
http://dx.doi.org/10.1016/j.ejmech.2013.09.009
---------- VANCOUVER ----------
Elicio, P.D., Chao, M.N., Galizzi, M., Li, C., Szajnman, S.H., Docampo, R., et al. Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents. Eur. J. Med. Chem. 2013;69:480-489.
http://dx.doi.org/10.1016/j.ejmech.2013.09.009