Design, Synthesis and Biological Evaluation of Ketoprofen Conjugated To RGD/NGR for Targeted Cancer Therapy.

Abstract

It is well known that Arginine-Glycine-Aspartic acid (RGD) and Asparagine-Glycine-Arginine (NGR) peptides preferentially bind to integrin receptors and aminopeptidase N respectively and these two receptors play important roles in angiogenesis. Therefore ketoprofen as a non-selective cox Inhibitor was conjugated with linear RGD and NGR to take advantage of targeting capability of these two motifs and delivering ketoprofen to these cancer cells with overexpression of integrin and aminopeptidase N. In order to investigate the impact of possible steric hindrance due to the attachment of the drug to the peptide, a linear six carbon (hexanoic acid) linker was also used as a spacer. Cytotoxic effect of the synthesized compounds was evaluated against a group of cancer cell lines, including MCF-7, A2780 (αvβ3 positive), OVCAR3 (high αvβ3), HT-1-80 (high CD13) and SKOV-3 (CD13 positive). Both NGR and RGD conjugated forms of ketoprofen showed higher cytotoxic activity against OVCAR3 and HT-1-80 respectively.