Mahmoud Sahar, Aboul-Fadl Tarek, Sheha Mahmoud, Farag Hassan, Mouhamed Abdel-Maaboud I
Dept.Pharm.Med.Chem., Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
Arch Pharm (Weinheim). 2003 Dec;336(12):573-84. doi: 10.1002/ardp.200300808.
In order to overcome the slow oxidation of 1, 2-dihydro-N-alkylisoquinoline, 1, 2-dihydroisoquinoline-N-acetic acid derivatives (3b-d) were designed and synthesized as new chemical delivery systems (CDS) for the brain. Molecular orbital calculations for the suggested derivatives revealed that these carriers are stable against oxidation. However, hydrolysis to their corresponding anions will accelerate the rate of oxidation, and accordingly increase the efficiency of brain specific delivery. A multivariate calibration method for in vitro determination of the oxidation rate for the suggested brain specific chemical delivery system is described. The method is based on measurement of individual rates of oxidation of prepared 1, 2-dihydroisoquinolines, using silver ions to provide the corresponding quaternary forms. Components of binary mixtures formed through the oxidation step (composed of the dihydro-compound and its quaternary form), showed a considerable degree of spectral overlapping - more than 90% in all cases. Resolution of these binary mixtures under investigation has been accomplished mainly using classical least squares analysis. Kinetic oxidation data of the tested compounds revealed that these new CDSs have a reasonable oxidation rate for efficient brain delivery.
为了克服1,2 - 二氢 - N - 烷基异喹啉的缓慢氧化问题，设计并合成了1,2 - 二氢异喹啉 - N - 乙酸衍生物（3b - d）作为新型脑靶向化学传递系统（CDS）。对所建议衍生物的分子轨道计算表明，这些载体对氧化具有稳定性。然而，水解成相应的阴离子会加速氧化速率，从而提高脑靶向递送的效率。描述了一种用于体外测定所建议的脑靶向化学传递系统氧化速率的多元校准方法。该方法基于测量制备的1,2 - 二氢异喹啉的个体氧化速率，使用银离子生成相应的季铵盐形式。通过氧化步骤形成的二元混合物的组分（由二氢化合物及其季铵盐形式组成）在所有情况下都显示出相当程度的光谱重叠——超过90%。对这些研究中的二元混合物的解析主要采用经典最小二乘法完成。测试化合物的氧化动力学数据表明，这些新型CDS具有合理的氧化速率，可实现高效的脑递送。
