title: Synthesis, characterisation and biological evaluation of N-(ferrocenyl)naphthoyl amino acid esters as anticancer agents.
abstract: A series of N-(ferrocenyl)naphthoyl amino acid esters 5-18 has been prepared by coupling ferrocenyl naphthoic acids 3-4 to alpha-amino acids and linear amino acids in the presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBt). The compounds were fully characterised by a range of NMR spectroscopic techniques, UV-Vis spectroscopy, mass spectrometry and cyclic voltammetry. X-ray crystallographic studies of the intermediate compounds 1-2 were also performed. Biological evaluation of the intermediates 1-2 and N-(ferrocenyl)naphthoyl amino acid esters 5-18 was performed in the H1299 non-small cell lung cancer (NSCLC) cell line and the Sk-Mel-28 metastatic melanoma cell line. The intermediates 1-2 failed to produce an effect in either cell line. Compounds 5-18 exhibited a strong anti-proliferative effect in the H1299 cell line, whilst the Sk-Mel-28 cells were slightly more resistant to these compounds. N-(6-ferrocenyl-2-naphthoyl)-gamma-aminobutyric acid ethyl ester 17 shows a particularly high activity in both the H1299 cell line (IC(50) = 0.62 +/- 0.07 microM) and the Sk-Mel-28 cell line (IC(50) = 1.41 +/- 0.04 microM).
authors.affiliation: School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland.
authors.forename: Aine
authors.initials: A
authors.lastname: Mooney
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Corry
authors.forename: Cliodhna
authors.initials: C
authors.lastname: Ní Ruairc
authors.forename: Thamir
authors.initials: T
authors.lastname: Mahgoub
authors.forename: Dermot
authors.initials: D
authors.lastname: O'Sullivan
authors.forename: Norma
authors.initials: N
authors.lastname: O'Donovan
authors.forename: John
authors.initials: J
authors.lastname: Crown
authors.forename: Sunil
authors.initials: S
authors.lastname: Varughese
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Draper
authors.forename: Dilip K
authors.initials: DK
authors.lastname: Rai
authors.forename: Peter T M
authors.initials: PT
authors.lastname: Kenny
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D055664:Electrochemical Techniques; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D008968:Molecular Conformation
chemical_list: D000970:Antineoplastic Agents; D005296:Ferrous Compounds; C553997:N-(6-ferrocenyl-2-naphthoyl)-gamma-aminobutyric acid ethyl ester