Novel tamoxifen-based drug leads: synthesis, metal complex formation and docking studies towards improved breast cancer treatment

Alenazi, Tareq 2025. Novel tamoxifen-based drug leads: synthesis, metal complex formation and docking studies towards improved breast cancer treatment. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

There is an increasing interest in the development of tamoxifen derivatives that exhibit enhanced anticancer activity, stability, and selectivity. Tamoxifen is a commonly prescribed treatment for estrogen receptor-positive breast cancer; however, its prolonged administration may result in resistance and adverse effects. The objective of this research was to create novel Schiff base ligands that were constructed using the tamoxifen scaffold and contained two or more nitrogen donor atoms to facilitate coordination with transition metals. Additionally, the potential anticancer activity of the resulting metal complexes was assessed, and their interactions with breast cancer-related targets were assessed through molecular docking studies. In Chapter 2, three novel tamoxifen-based ligands were synthesised and fully characterised. Each ligand was then reacted with a series of divalent metal salts Pt(II), Cu(II), Co(II), Ni(II), and Zn(II) to form stable 2:1 (ligand-to-metal) coordination complexes. The products were characterised using NMR, IR, UV-Vis, and mass spectrometry to confirm their structures and purity. Chapter 3 describes the synthesis of two additional Schiff base ligands with structural modifications designed to improve coordination ability and biological activity. Each ligand formed five new metal complexes following the same synthetic strategy, and the compounds were subjected to full spectroscopic and analytical characterisation. In Chapter 4, a final Schiff base ligand was prepared and reacted with the same set of metal salts. The resulting five metal complexes were characterised and compared with previous analogues to understand the influence of structural changes on coordination behaviour and spectral properties. Chapter 5 presents molecular docking studies using AutoDock 4, which were performed for all synthesised ligands and their metal complexes. These were docked against estrogen receptor alpha (ERα) and other breast cancer-relevant proteins to predict binding modes and relative affinities. An additional 21 derivatives were modelled to support structure–activity relationship (SAR) insights. Chapter 6 summarises the main findings and discusses the contribution of this work toward developing new tamoxifen-inspired metal complexes as potential candidates for targeted breast cancer therapy.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Chemistry
Date of First Compliant Deposit:	6 May 2026
Last Modified:	25 Aug 2026 21:44
URI:	https://orca.cardiff.ac.uk/id/eprint/186814

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