Harry, Andy Garry (2013) The synthesis, structural characterization and in vitro anticancer activity of novel ferrocenyl bioconjugates. PhD thesis, Dublin City University.
Abstract
A series of 1-alkyl-1’-N-para, N-meta and N-ortho-(ferrocenyl) benzoyl dipeptide esters and N-{para-(ferrocenyl) ethynyl benzoyl}, N-{6-(ferrocenyl) ethynyl-2-naphthoyl} and N-{5-(ferrocenyl) ethynyl-2-furanoyl} amino acid and dipeptide esters were prepared. The novel ferrocenyl based bioconjugates were prepared by coupling 1-alkyl-1’-N-para, N-meta and N-ortho-(ferrocenyl) benzoic acid and N-{para-(ferrocenyl) ethynyl benzoyl}, N-{6-(ferrocenyl) ethynyl-2-naphthoyl} and N-{5-(ferrocenyl) ethynyl-2-furanoyl} benzoic acid to α-amino acid ethyl esters and dipeptide ethyl esters using the conventional N-(3-dimethylaminopropyl)-N’-ethylcarbodiimidehydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) protocol. The new classes of compounds were characterized by a combination of 1H NMR, 13C NMR, DEPT-135 and 1H-13C COSY (HMQC) spectroscopy, electrospray ionization mass spectrometry (ESI-MS). Biological evaluation of the 1-alkyl-1’-N-para, N-meta and N-ortho-(ferrocenyl) benzoyl dipeptide esters were carried out in the H1299 non-small cell lung cancer (NSCLC) cells.
The most active derivatives of the 1-alkyl-1’-N-para, N-meta and N-ortho-(ferrocenyl) benzoyl dipeptide esters are the 1-methyl-1’-N-{para-(ferrocenyl) benzoyl} glycine glycine ethyl ester with an IC50 value of 2.8 ± 1.23 µM, the 1-ethyl-1’–N-{para-(ferrocenyl) benzoyl} glycine glycine ethyl ester with an IC50 value of 3.5 ± 0.82 µM and the 1-methyl-1’-N-{meta-(ferrocenyl) benzoyl} glycine glycine ethyl ester with an IC50 of 2.6 ± 0.62 µM and these derivatives are more cytotoxic in vitro than the clinically employed anti-cancer drug carboplatin. In addition, these compounds display improved bioactivity in comparison to the corresponding most active benzoyl analogues which were the N-{meta-(ferrocenyl) benzoyl} glycine L-alanine ethyl ester and N-{para-(ferrocenyl) benzoyl} glycine L-alanine ethyl ester which displayed IC50 values of 4.0 µM and 6.6 µM respectively
The biological evaluation of N-{para-(ferrocenyl) ethynyl benzoyl}, N-{6-(ferrocenyl) ethynyl-2-naphthoyl} and N-{5-(ferrocenyl) ethynyl-2-furanoyl} amino acid and dipeptide esters were also carried out in the H1299 non-small cell lung cancer (NSCLC) cells. The most active derivatives of the N-{para-(ferrocenyl) ethynyl benzoyl}, N-{6-(ferrocenyl) ethynyl-2-naphthoyl} and N-{5-(ferrocenyl) ethynyl-2-furanoyl} amino acid and dipeptide esters are the N-{para-(ferrocenyl) ethynyl benzoyl} glycine L-alanine ethyl ester with an IC50 value of 3.8 ± 1.92 µM and the N-{6-(ferrocenyl) ethynyl-2-naphthoyl} sarcosine L-alanine ethyl ester with an IC50 value of 3.2 ± 2.64 µM. These compounds are more active than carboplatin with an IC50 value of 10 ± 1.60 µM but are less effective than cisplatin with an IC50 value of 1.5 ± 0.10 µM which are clinically employed anti-cancer drugs. However, the presence of the ethynyl moiety had a negative effect of anti-proliferative effect compared to analogous compounds prepared previously lacking the ethynyl group. For example for N-{6-(ferrocenyl) ethynyl-2-naphthoyl} γ-aminobutyric acid ethyl ester the IC50 value is 7.2 ± 1.51 µM whereas for N-(6-ferrocenyl-2-naphthoyl) γ-aminobutyric acid ethyl ester the IC50 value was 0.62 ± 0.03 µM
Metadata
Item Type: | Thesis (PhD) |
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Date of Award: | March 2013 |
Refereed: | No |
Supervisor(s): | Kenny, Peter T.M. |
Uncontrolled Keywords: | Ferrocene; Bioorganometallic chemistry; Dipeptides; Cytotoxicity; Lung cancer |
Subjects: | Physical Sciences > Chemistry |
DCU Faculties and Centres: | DCU Faculties and Schools > Faculty of Science and Health > School of Chemical Sciences |
Use License: | This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. View License |
ID Code: | 17742 |
Deposited On: | 05 Apr 2013 11:12 by Peter Kenny . Last Modified 19 Jul 2018 14:58 |
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