ATLA::Alternatives to Laboratory Animals

Volume 26, Number 5

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

ATLA 26, 635-647, September/October 1998

Mario Gonzalez-De La Parra,1 Carlos Ramos-Mundo,2 Manuel Jimenez-Estrada,3 Claudia Ponce-De Leon,1 Veronica Tejeda,1 Karla G. Cuevas1 and Raul G. Enriquez3

1Departamento de Farmacia, Facultad de Quimica, UNAM, CU, Mexico, DF 04510 Mexico; 2Departamento de Sistemas Biologicos, Universidad Autonoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Coyoacan, DF 04960 Mexico; 3Instituto de Quimica, UNAM, CU, Mexico, DF 04510 Mexico

SUMMARY

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-a-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-β-naphthaleneethanol), and their racemic mixtures, inhibited the radicle growth of R. sativus at a concentration of 1 mM, 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 6methoxy-a-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 0.5 mM. It was found that they did not inhibit either the radicle or the hypocotyl growth of R. sativus.

Keywords: toxicological screening system, factorial design, naproxen, naproxol, naproxen naproxyl esters, Raphanus sativus L