Gonzalez-de la Parra M, Ramos-Mundo C, Jimenez-Estrada M, Ponce-de Leon C, Castillo R, Tejeda V, Cuevas K G, Enriquez R G
Departamento de Farmacia, Facultad de Quimica, UNAM, CU Mexico, Mexico.
Departamento de Sistemas Biologicos, Universidad Autonoma Metropolitana-Xochimilco, Coyoacan, Mexico.
Altern Lab Anim. 1998 Sep-Oct;26(5):635-47.
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.
开发了一种用萝卜（Raphanus sativus L.）种子进行的发芽生物测定法，作为一种毒理学筛选系统，用于评估萘普生新潜在前药的效果，以替代动物和动物细胞毒性筛选。萘普生（6-甲氧基-α-甲基-2-萘乙酸）和萘普生醇（6-甲氧基-β-2-萘乙醇）的两种对映体及其外消旋混合物在浓度为1mM时均抑制萝卜胚根生长，而仅（R）-（+）-萘普生醇和外消旋萘普生醇在相同浓度下抑制萝卜下胚轴生长。合成了由萘普生和萘普生醇之间的酯化反应的组合化学产生的四种新型组合酯，即萘普生萘普生酯（6-甲氧基-β-甲基-2-萘乙基6-甲氧基-α-甲基-2-萘乙酸酯），然后在发芽生物测定法中以0.5mM的浓度进行测试。发现它们既不抑制萝卜胚根也不抑制下胚轴生长。
