RESUMO
A germination bioassay employing radish (Raphanus sativus L.) seeds was used for the identification and quantification of the synergistic or antagonistic effects of equimolar binary mixtures formed by the combination of (S)-naproxen, (S)-ibuprofen, (S)-naproxol and (S)-ibuprofen alcohol, by using an approach based on experiments with mixtures. Synergistic effects were found to be statistically significant for the radicle growth of the binary mixtures formed by the combination of (S)-naproxol with (S)-naproxen, and (S)-naproxol with (S)-ibuprofen alcohol. These findings might indicate the existence of the corresponding potential drug-drug interactions. However, due to the complexity of the biological processes in humans and the fact that the correlation between this bioassay and human biological activity has not yet been established, further studies with other organisms or test systems are necessary to confirm the existence of these drug-drug interactions.
RESUMO
A germination bioassay with radish (Raphanus sativus L.) seeds was developed as a toxicological screening system for assessing the effects of new potential prodrugs of naproxen, as an alternative to animals and animal cell toxicity screens. Both enantiomers of naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-ß-2-naphthaleneethanol), and their racemic mixtures, inhibited the radicle growth of R. sativus at a concentration of 1mM, while only (R)-(+ )-naproxol and racemic naproxol inhibited the hypocotyl growth of R. sativus at the same concentration. Four novel combinatorial esters, naproxen naproxyl esters (6-methoxy-ß-methyl-2-naphthaleneethyl 6-methoxy-α-methyl-2-naphthaleneacetate), resulting from the combinatorial chemistry of the esterification reaction between naproxen and naproxol, were synthesised and then tested in the germination bioassay, at a concentration of 0.5mM. It was found that they did not inhibit either the radicle or the hypocotyl growth of R. sativus.