title: Anti-cancer activity of an acid-labile N-alkylisatin conjugate targeting the transferrin receptor.
abstract: We have previously reported a series of pH-sensitive imine-linked N-alkylisatin prodrugs that are stable at pH 7.4, but readily cleaved at pH 4.5. Herein, one of the most potent prodrugs, 5,7-dibromo-N-(p-methoxybenzyl)isatin (NAI), was functionalized with a para-phenylpropionic acid linker, and the resulting NAI-imine prodrug conjugated to transferrin (Tf) to form a NAI-imine-Tf conjugate. Cytotoxicity assays revealed the conjugate was equipotent to the free drug against MCF-7 breast cancer cells, with clear selectivity patterns based on TfR levels. These results suggest that this novel isatin-based cytotoxin conjugated to a tumor targeting protein via an acid-labile linker warrants further preclinical testing.
authors: School of Biological Sciences and Center for Medical Bioscience, University of Wollongong, Australia.
authors: Vineesh
authors: V
authors: Indira Chandran
authors: Lidia
authors: L
authors: Matesic
authors: Julie M
authors: JM
authors: Locke
authors: Danielle
authors: D
authors: Skropeta
authors: Marie
authors: M
authors: Ranson
authors: Kara L
authors: KL
authors: Vine
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007510:Isatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D058990:Molecular Targeted Therapy / Q000379:methods; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D011990:Receptors, Transferrin; D007510:Isatin