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

Authors

  • Afshin Zarghi Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Bahareh Shokri Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Farzad Kobarfard Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Reza Mohammadi Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Soraya Shahhosseini Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:

It is well known that Arginine-Glycine-Aspartic acid (RGD) and Asparagine-Glycine-Arginine (NGR) peptides preferentially bind to integrin receptors and aminopeptidase Nrespectively and these two receptors play important roles in angiogenesis. Therefore ketoprofenas a non-selective cox Inhibitor was conjugated with linear RGD and NGR to take advantageof targeting capability of these two motifs and delivering ketoprofen to these cancer cellswith overexpression of integrin and aminopeptidase N. In order to investigate the impact ofpossible 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 compoundswas 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 andRGD conjugated forms of ketoprofen showed higher cytotoxic activity against OVCAR3 andHT-1-80 respectively.

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Journal title

volume 17  issue 4

pages  1297- 1305

publication date 2018-10-01

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