A germination bioassay as a toxicologial screening system for studying the effects of potential prodrugs of naproxen

By Gonzalex-de la Parra, M. - Ramos-Mundo, C. - Jimenez-Estrada, M. - Ponce-de Leon, C. - Castillo, R. - Tejeda, V. - Cuevas, K.G. - Enriquez, R.G.

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-alpha-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-beta-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-beta-methyl-2-naphthaleneethyl 6-methoxy-alpha-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.