Title

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

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

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Link to publisher version (DOI)

http://dx.doi.org/10.1016/j.bmc.2011.01.015