Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi

Journal of Medicinal Chemistry
G M CinqueE G Gros

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 the 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 IC50 of 2.2 microM. 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...Continue Reading

References

Oct 1, 1990·Revista Da Sociedade Brasileira De Medicina Tropical·H de O Ferreira
Jan 1, 1973·Annual Review of Microbiology·Z Brener
Jul 1, 1981·Molecular and Biochemical Parasitology·R DocampoA O Stoppani
Mar 1, 1980·The American Journal of Tropical Medicine and Hygiene·G A SchmuñisJ M Peralta
Jan 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·E A VladusicE H Charreau
Aug 1, 1994·The Journal of Steroid Biochemistry and Molecular Biology·E A VladusicE H Charreau
Mar 4, 1994·Journal of Medicinal Chemistry·C Gallo-RodriguezP J van Galen
Mar 1, 1996·Transfusion·S A Galel, L V Kirchhoff
Apr 1, 1997·Parasitology Today·R Docampo, G A Schmuñis

❮ Previous
Next ❯

Citations

Oct 5, 2013·European Journal of Medicinal Chemistry·Pablo D ElicioJuan B Rodriguez
Mar 30, 2001·Bioorganic & Medicinal Chemistry Letters·S H SzajnmanJ B Rodriguez
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·J B RodriguezE G Gros
Mar 29, 2000·The International Journal of Biochemistry & Cell Biology·C F BernardesA E Vercesi
Apr 11, 2012·Journal of Medicinal Chemistry·Fu-Yang LinEric Oldfield
Jul 29, 2005·Antimicrobial Agents and Chemotherapy·Olga SenkovichDebasish Chattopadhyay
Jun 1, 2000·Experimental Parasitology·E DeharoV R Gordeuk
Dec 25, 2015·The Journal of Organic Chemistry·Igors Sokolovs, Edgars Suna
Jun 24, 2009·Experimental Parasitology·Roman MezencevRoberto Docampo
Jul 5, 2016·Expert Opinion on Therapeutic Patents·Juan B RodriguezSergio H Szajnman
Jan 6, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tamila GalakaJuan B Rodriguez
May 7, 2002·Memórias do Instituto Oswaldo Cruz·José Rodriques Coura, Solange L de Castro
Mar 13, 2012·Expert Opinion on Therapeutic Patents·Juan Bautista Rodriguez, Sergio Hernán Szajnman
Aug 15, 2019·Expert Opinion on Drug Discovery·Fernando Villalta, Girish Rachakonda
Jun 20, 2020·Archiv der Pharmazie·Angeliki P Kourounakis, Eugenia Bavavea
Feb 28, 2019·Bioorganic & Medicinal Chemistry·María N ChaoJuan B Rodriguez
Aug 23, 2002·Journal of Medicinal Chemistry·Eleonora ElhalemJuan B Rodriguez
Apr 14, 2011·The Journal of Organic Chemistry·Manuel A V Ribeiro da SilvaÁlvaro Cimas
Sep 8, 2006·The Journal of Physical Chemistry. B·Verónica Muriel SanchezAdrián Gustavo Turjanski

❮ Previous
Next ❯

Related Concepts