title: Synthesis and hydrolytic evaluation of acid-labile imine-linked cytotoxic isatin model systems.
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.
authors.affiliation: School of Chemistry, University of Wollongong, Wollongong, NSW, Australia.
authors.forename: Lidia
authors.initials: L
authors.lastname: Matesic
authors.forename: Julie M
authors.initials: JM
authors.lastname: Locke
authors.forename: Kara L
authors.initials: KL
authors.lastname: Vine
authors.forename: Marie
authors.initials: M
authors.lastname: Ranson
authors.forename: John B
authors.initials: JB
authors.lastname: Bremner
authors.forename: Danielle
authors.initials: D
authors.lastname: Skropeta
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007510:Isatin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008223:Lymphoma / Q000188:drug therapy*; D008954:Models, Biological; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D007097:Imines; D007510:Isatin