School of Chemistry, University of Wollongong, Wollongong, NSW, Australia.
Bioorg Med Chem. 2011 Mar 1;19(5):1771-8. doi: 10.1016/j.bmc.2011.01.015. Epub 2011 Jan 14.
In this study a series of isatin-based, pH-sensitive aryl imine derivatives with differing aromatic substituents and substitution patterns were synthesised and their acid-catalysed hydrolysis evaluated. These derivatives were functionalised at the C3 carbonyl group of a potent N-substituted isatin cytotoxin and were stable at physiological pH but readily cleaved at pH 4.5. Observed rates of hydrolysis for the embedded imine-acid moiety were in the order para-phenylpropionic acid>phenylacetic acid (para>meta)>benzoic acid (meta>para). The ability to fine-tune hydrolysis rates in this way has potential implications for optimising imine linked, tumour targeting cytotoxin-protein conjugates.
在这项研究中，合成了一系列基于靛红的、对 pH 敏感的芳基亚胺衍生物，它们具有不同的芳基取代基和取代模式，并对其酸催化水解进行了评估。这些衍生物在有效的 N-取代靛红细胞毒素的 C3 羰基上进行了功能化，在生理 pH 下稳定，但在 pH 4.5 时容易断裂。嵌入的亚胺-酸部分的水解速率顺序为对-苯丙酸>苯乙酸（对>间）>苯甲酸（间>对）。以这种方式精细调整水解速率的能力可能对优化亚胺连接的、针对肿瘤的细胞毒素-蛋白缀合物具有重要意义。
