Anti-cancer activity of an acid-labile N-alkylisatin conjugate targeting the transferrin receptor

Authors

Vineesh Indira Chandran, University of WollongongFollow
Lidia Matesic, University of WollongongFollow
Julie M. Locke, University of WollongongFollow
Danielle Skropeta, University of WollongongFollow
Marie Ranson, University of WollongongFollow
Kara L. Vine, University of WollongongFollow

RIS ID

52473

Publication Details

Indira Chandran, V., Matesic, L., Locke, J. M., Skropeta, D., Ranson, M. & Vine, K. L. (2012). Anti-cancer activity of an acid-labile N-alkylisatin conjugate targeting the transferrin receptor. Cancer Letters, 316 (2), 151-156.

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-(pmethoxybenzyl) 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.