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Cinque, G.M.; Szajnman, S.H.; Zhong, L.; Docampo, R.; Schvartzapel, A.J.; Rodriguez, J.B.; Gros, E.G. "Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi" (1998) Journal of Medicinal Chemistry. 41(9):1540-1554
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Abstract:

Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related structures were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class of drugs was envisioned by modifying the nonpolar 4-phenoxyphenoxy moiety replacing selected aromatic protons by different groups via electrophilic aromatic substitution reactions as well as introducing a sulfur atom at file polar extreme. Of the designed compounds, sulfur-containing derivatives were shown to be potent antireplicative agents against T. cruzi. Among these drugs, 4-phenoxyphenoxyethyl thiocyanate (compound 56) proved to be an extremely active growth inhibitor of the epimastigote forms of T. cruzi and displayed an IC500 of 2.2 μM. Under the same assay conditions, this drug was much more active than Nifurtimox, one of the drugs currently in clinical use to control this disease. This thiocyanate derivative was also a very active inhibitor against the intracellular form of the parasite at the nanomolar level. Other sulfur derivatives prepared also exhibited very potent antiproliferative action against T. cruzi. The presence of a sulfur atom at the polar extreme for this family of compounds seems to be very important for biological action because this atom was always associated with high inhibition values. 4-Phenoxyphenoxyethyl thiocyanate presents very good prospective not only as a lead drug but also as a potential chemotherapeutic agent.

Registro:

Documento: Artículo
Título:Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi
Autor:Cinque, G.M.; Szajnman, S.H.; Zhong, L.; Docampo, R.; Schvartzapel, A.J.; Rodriguez, J.B.; Gros, E.G.
Filiación:Depto. de Quim. Orgánica, Fac. de Ciencias Exactas y Naturales, Ciudad Universitaria, 1428 Buenos Aires, Argentina
Laboratory of Molecular Parasitology, College of Veterinary Medicine, Univ. Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61801, United States
Palabras clave:4 phenoxyphenoxyethyl thiocyanate; nifurtimox; unclassified drug; article; chagas disease; drug screening; drug structure; drug synthesis; epimastigote; trypanosoma cruzi; Animals; Drug Evaluation, Preclinical; Nifurtimox; Phenyl Ethers; Structure-Activity Relationship; Thiocyanates; Trypanocidal Agents; Trypanosoma cruzi
Año:1998
Volumen:41
Número:9
Página de inicio:1540
Página de fin:1554
DOI: http://dx.doi.org/10.1021/jm970860z
Título revista:Journal of Medicinal Chemistry
Título revista abreviado:J. Med. Chem.
ISSN:00222623
CODEN:JMCMA
CAS:4-phenoxyphenoxyethyl thiocyanate; Nifurtimox, 23256-30-6; Phenyl Ethers; Thiocyanates; Trypanocidal Agents
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222623_v41_n9_p1540_Cinque

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Citas:

---------- APA ----------
Cinque, G.M., Szajnman, S.H., Zhong, L., Docampo, R., Schvartzapel, A.J., Rodriguez, J.B. & Gros, E.G. (1998) . Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi. Journal of Medicinal Chemistry, 41(9), 1540-1554.
http://dx.doi.org/10.1021/jm970860z
---------- CHICAGO ----------
Cinque, G.M., Szajnman, S.H., Zhong, L., Docampo, R., Schvartzapel, A.J., Rodriguez, J.B., et al. "Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi" . Journal of Medicinal Chemistry 41, no. 9 (1998) : 1540-1554.
http://dx.doi.org/10.1021/jm970860z
---------- MLA ----------
Cinque, G.M., Szajnman, S.H., Zhong, L., Docampo, R., Schvartzapel, A.J., Rodriguez, J.B., et al. "Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi" . Journal of Medicinal Chemistry, vol. 41, no. 9, 1998, pp. 1540-1554.
http://dx.doi.org/10.1021/jm970860z
---------- VANCOUVER ----------
Cinque, G.M., Szajnman, S.H., Zhong, L., Docampo, R., Schvartzapel, A.J., Rodriguez, J.B., et al. Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi. J. Med. Chem. 1998;41(9):1540-1554.
http://dx.doi.org/10.1021/jm970860z