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

Journal Article


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

Publication Date


  • 2011

Citation


  • 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.

Scopus Eid


  • 2-s2.0-79952195584

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/3759

Number Of Pages


  • 7

Start Page


  • 1771

End Page


  • 1778

Volume


  • 19

Issue


  • 5

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

Publication Date


  • 2011

Citation


  • 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.

Scopus Eid


  • 2-s2.0-79952195584

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/3759

Number Of Pages


  • 7

Start Page


  • 1771

End Page


  • 1778

Volume


  • 19

Issue


  • 5