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Novel heterocyclic functionalised ferrocenyl derivatives as potential anti-cancer agents

Ontiveros Castillo, Karen Guadalupe (2019) Novel heterocyclic functionalised ferrocenyl derivatives as potential anti-cancer agents. PhD thesis, Dublin City University.

Abstract
Earlier in vitro studies have shown that ferrocenyl amino acid and dipeptide bioconjugates exhibit anti-proliferative activity against the lung cancer cell lines H1299 and A549, the melanoma cell lines SK-MEL-28, HT-144, MalMe-3M and Lox-IMVI, and the breast cancer cell line MCF-7. The aim of this research was to further explore the structure- activity relationship (SAR) of ferrocenyl compounds other than amino acid bioconjugates. Thus, a series of novel heterocyclic functionalised ferrocenyl derivatives has been synthesized, characterized and biologically evaluated for their anti-proliferative activity and interaction with DNA. The synthesis was achieved by the conventional N-(3- dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and N- hydroxysuccinimide (NHS) coupling protocol. Characterisation was completed by a range of techniques including NMR (1H, 13C, DEPT-135, COSY, HSQC, HMBC), IR, UV-Vis, MS, elemental analysis and X-rays crystallography. For the in vitro anti-proliferative evaluation, compounds were tested against the human cervical carcinoma cell line SiHa (ATCC® HTB-35TM) and the human liver cell line Chang (ATCC® CCL-13TM) via the WST-1 assay. Suitable candidates were then examined for potential DNA binding and damaging properties. The anti-proliferative activity of additional derivatives previously developed by this group is also reported; these compounds belong to the series of N-(1′- alkyl-6-ferrocenyl-2-naphthoyl) amino acid and dipeptide esters and N- (ferrocenylmethylamino acid) fluorinated benzene carboxamides. Compounds N-(1′- ethyl-6-ferrocenyl-2-naphthoyl)-glycine-D-alanine ethyl ester, N-(ferrocenylmethyl-L- norleucine)-3,4,5-trifluorobenzene carboxamide and N-(ferrocenylmethyl-L-(+)-alpha- phenylglycine)-2,3,4,5,6-pentafluorobenzene carboxamide have shown to be significantly more cytotoxic against SiHa cells than chemotherapeutic control drugs vincristine and cisplatin, whilst maintaining a moderate percentage of viability on Chang cells. The overall results suggest that some ferrocenyl derivatives analysed are promising anticancer agents worthy of future therapeutic analysis.
Metadata
Item Type:Thesis (PhD)
Date of Award:November 2019
Refereed:No
Supervisor(s):Kellett, Andrew
Uncontrolled Keywords:Chemotherapy
Subjects:Medical Sciences > Cancer
Physical Sciences > Chemistry
Physical Sciences > Inorganic chemistry
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Chemical Sciences
Research Initiatives and Centres > National Institute for Cellular Biotechnology (NICB)
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. View License
Funders:National Council of Science and Technology (CONACYT) Mexico, Instituto de Innovación y Transferencia de Tecnología (i2t2) Mexico, State of Nuevo León Mexico (grant #399856)
ID Code:23750
Deposited On:28 Nov 2019 13:58 by Andrew Kellett . Last Modified 14 Sep 2021 03:30
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