Anti-cancer activity of an acid-labile N-alkylisatin conjugate targeting the transferrin receptorFaculty of Science - Papers (Archive)
AbstractWe 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.
Citation InformationVineesh Indira Chandran, Lidia Matesic, Julie M Locke, Danielle Skropeta, et al.. "Anti-cancer activity of an acid-labile N-alkylisatin conjugate targeting the transferrin receptor" (2012) p. 151 - 156
Available at: http://works.bepress.com/skropeta/23/