7452-11-1Relevant articles and documents
In vitro and in vivo trypanocidal activities of 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-cromen-2-one, a new synthetic coumarin of low cytotoxicity against mammalian cells
Brancaglion, Guilherme Andrade,Toyota, André Eidi,Cardoso Machado, José Vaz,Fernandes Júnior, Ant?nio ávila,Silveira, Alberto Thalison,Vilas Boas, Diego Fernandes,dos Santos, Elda Gon?alves,Caldas, Ivo Santana,Carvalho, Diogo Teixeira
, p. 1888 - 1898 (2018)
Natural and synthetic coumarins have been described as prototypes of new drug candidates against Chagas’ disease. During a typical screening with new compounds, we observed the potential of a new synthetic nitrobenzoylcoumarin (1) as trypanocidal against Trypanosoma cruzi epimastigotas. Then, we decided to prepare and evaluate a set of analogues from 1 to check the major structural requirements for trypanocidal activity. The structural variations were conducted in six different sites on the original compound and the best derivative (3) presented activity (IC50 28?±?3?μM) similar to that of benznidazole (IC50 25?±?10?μM). The enhancement of trypanocidal activity was conditioned to a change in the side chain at C6 (allyl to n-propyl group) and the preservation of coumarin nucleus and the nitrobenzoyl group at C3. Exposure of 3 to H9C2 cells showed low toxicity (CC50?>?200?μM) and its activity on T.?cruzi amastigotes (IC50 13?±?0.3?μM) encouraged us to perform an evaluation of its potential when given orally to mice infected with trypomastigote forms. Derivative 3 was able to reduce parasitemia when compared to the group of untreated animals. Taken together, these results show the potential therapeutic application of the synthetic coumarins.
