factorial design

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A Germination Bioassay as a Toxicological Screening System for Studying the Effects of Potential Prodrugs of Naproxen

Mario Gonzalez-de la Parra, Carlos Ramos-Mundo, Manuel Jimenez-Estrada, Claudia Ponce-de Leon, R. Castillo, Veronica Tejeda, Karla G. Cuevas and Raul G. Enriquez

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-β−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-β−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.
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