Synthesis and hydrolytic evaluation of acid-labile imine-linked cytoxic isatin model systems

Authors

Lidia Matesic, University of WollongongFollow
Julie Locke, University of WollongongFollow
Kara L. Perrow, University of WollongongFollow
Marie Ranson, University of WollongongFollow
John B. Bremner, University of WollongongFollow
Danielle Skropeta, University of WollongongFollow

RIS ID

35080

Publication Details

Matesic, L., Locke, J. M.., Vine, K. L., Ranson, M., Bremner, J. B. & Skropeta, D. (2011). Synthesis and hydrolytic evaluation of acid-labile imine-linked cytoxic isatin model systems. Bioorganic & Medicinal Chemistry, 19 (5), 1771-1778.

Abstract

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