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Design, Synthesis and Biological Evaluation of Ketoprofen Conjugated To RGD/NGR for Targeted Cancer Therapy
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 wa...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shaheed Beheshti University of Medical Sciences
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269559/ https://www.ncbi.nlm.nih.gov/pubmed/30568688 |
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author | Shokri, Bahareh Zarghi, Afshin Shahhoseini, Soraya Mohammadi, Reza Kobarfard, Farzad |
author_facet | Shokri, Bahareh Zarghi, Afshin Shahhoseini, Soraya Mohammadi, Reza Kobarfard, Farzad |
author_sort | Shokri, Bahareh |
collection | PubMed |
description | 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 (α(v)β(3) positive), OVCAR3 (high α(v)β(3)), 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. |
format | Online Article Text |
id | pubmed-6269559 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Shaheed Beheshti University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-62695592018-12-19 Design, Synthesis and Biological Evaluation of Ketoprofen Conjugated To RGD/NGR for Targeted Cancer Therapy Shokri, Bahareh Zarghi, Afshin Shahhoseini, Soraya Mohammadi, Reza Kobarfard, Farzad Iran J Pharm Res Original Article 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 (α(v)β(3) positive), OVCAR3 (high α(v)β(3)), 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. Shaheed Beheshti University of Medical Sciences 2018 /pmc/articles/PMC6269559/ /pubmed/30568688 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Shokri, Bahareh Zarghi, Afshin Shahhoseini, Soraya Mohammadi, Reza Kobarfard, Farzad Design, Synthesis and Biological Evaluation of Ketoprofen Conjugated To RGD/NGR for Targeted Cancer Therapy |
title | Design, Synthesis and Biological Evaluation of Ketoprofen Conjugated To RGD/NGR for Targeted Cancer Therapy |
title_full | Design, Synthesis and Biological Evaluation of Ketoprofen Conjugated To RGD/NGR for Targeted Cancer Therapy |
title_fullStr | Design, Synthesis and Biological Evaluation of Ketoprofen Conjugated To RGD/NGR for Targeted Cancer Therapy |
title_full_unstemmed | Design, Synthesis and Biological Evaluation of Ketoprofen Conjugated To RGD/NGR for Targeted Cancer Therapy |
title_short | Design, Synthesis and Biological Evaluation of Ketoprofen Conjugated To RGD/NGR for Targeted Cancer Therapy |
title_sort | design, synthesis and biological evaluation of ketoprofen conjugated to rgd/ngr for targeted cancer therapy |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269559/ https://www.ncbi.nlm.nih.gov/pubmed/30568688 |
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