Allelochemical Activity of Eugenol-Derived Coumarins on Lactuca sativa L.

Coumarins are widely distributed substances in plant species that promote phytotoxic effects, allowing them to be exploited as herbicides less harmful to the environment, since many invasive species have demonstrated resistance to commercially available products. The derived coumarins used in this study had not been tested in plant models and their effect on plants was unknown. The objective of this study was to evaluate the phytotoxic action of these coumarins in bioassays with Lactuca sativa L., in order to select the most responsive substance whose toxicity was best elucidated by chromosomal complement and enzymatic antioxidant metabolism studies. From the phytotoxicity assays, coumarin 8-methoxy-2-oxo-6-(prop-2-en-1-yl)-2H-chromene-3-carboxylic acid (A1), reported here for the first time, was selected as the most responsive and caused a reduction in the following parameters: number of normal seedlings, fresh biomass, root length and shoot length. Subsequent studies demonstrated that this coumarin is cytogenotoxic due to damage caused to the cell cycle and the occurrence of chromosomal abnormalities. However, it did not interfere with antioxidant enzyme activity and did not cause lipid peroxidation. The changes caused by coumarin A1 described herein can contribute to better understanding the allelochemical actions of coumarins and the potential use of these substances in the production of natural herbicides.

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.

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.