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

Document Type: Research article


Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


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.


Main Subjects