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The synthesis, structural characterization and in vitro anticancer activity of novel ferrocenyl bioconjugates
Harry, Andy Garry
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
Keyword(s): Chemistry; Ferrocene; Bioorganometallic chemistry; Dipeptides; Cytotoxicity; Lung cancer
Publication Date:
2013
Type: Other
Peer-Reviewed: Unknown
Language(s): English
Contributor(s): Kenny, Peter T.M.
Institution: Dublin City University
Citation(s): Harry, Andy Garry (2013) The synthesis, structural characterization and in vitro anticancer activity of novel ferrocenyl bioconjugates. PhD thesis, Dublin City University.
Publisher(s): Dublin City University. School of Chemical Sciences
File Format(s): application/pdf
Related Link(s): http://doras.dcu.ie/17742/1/Andy_Garry_Harry_Thesis_2013.pdf
First Indexed: 2013-04-06 05:24:50 Last Updated: 2019-02-09 06:38:31