Back to Search
Start Over
Syntheses and in vitro antitumor activities of ferrocene-conjugated Arg-Gly-Asp peptides.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2012 Nov; Vol. 116, pp. 19-25. Date of Electronic Publication: 2012 Jul 02. - Publication Year :
- 2012
-
Abstract
- Ferrocene (Fc) and its conjugates have attracted considerable attention in recent years due to their unique electrochemical behavior and significant biological activities such as antitumor, antimalarial, and antifungal. Arg-Gly-Asp (RGD)-containing peptides, because of their selective binding to integrins which are highly expressed in tumor-induced angiogenesis, play a key role in cancer targeted therapy. In this study, Fc-RGD and Fc-Am-RGD (Fc: ferrocenoyl; Am: 6-aminohexanoic acid) conjugates were synthesized, and the antitumor activities in vitro were investigated. The cell uptake of the conjugates by B16 murine melanoma cells was measured using HPLC-electrochemical method. The antitumor activities of the conjugates were also evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric measurements. The experimental results revealed that Fc-RGD and Fc-Am-RGD exhibit more effective antitumor activities than their parent compounds RGD and Fc-COOH. Moreover, it is found that Fc-Am-RGD yields the lowest IC(50) values of 5.2 ± 1.4 μM toward B16 cells. The HPLC-electrochemical studies confirmed that the insertion of flexible alkyl spacer Am between Fc and RGD significantly increases the cell uptake toward B16 cells and consequently improves the antitumor activity. Our results suggest that Fc-RGD and Fc-Am-RGD conjugates are potential candidates for cancer treatment.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Line, Tumor
Flow Cytometry
Fluorescent Dyes
In Vitro Techniques
Magnetic Resonance Spectroscopy
Metallocenes
Mice
Oligopeptides pharmacology
Spectrometry, Mass, Electrospray Ionization
Antineoplastic Agents chemical synthesis
Antineoplastic Agents pharmacology
Ferrous Compounds chemistry
Oligopeptides chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 116
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23010325
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2012.06.014