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Synthesis of Thiourea and Guanidine Derivatives and Testing for Biological Activity

Thomas, Samuel (2019) Synthesis of Thiourea and Guanidine Derivatives and Testing for Biological Activity. Master of Science by Research (MScRes) thesis, University of Kent,. (KAR id:75616)

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Abstract

Thiourea and guanidine derivatives are versatile compounds that have previously been synthesised for use in a variety of industries from materials manufacturing to medical research. It is this versatility which interests us in new possible pathways for these compounds, with the focus being the potential for advanced oncology research. This thesis discusses a single project in two halves, the first synthesising thiourea and guanidine derivatives, whilst the second half looks at the biological activity of those target molecules on three different ovarian cancer cell lines. Once synthesised, the derivative compounds were fully characterised by ¹H NMR, ¹³C NMR, elemental analysis, mass spectrometry and melting point analysis. Four additional compounds were included for biological testing, which comprise of thiourea and guanidine iridium complexes with alternative uses in OLED technology, whose ligand environment may also provide biological activity in mammalian cell cultures. There were no specific biological targets in which we were attempting to challenge but treated this research as a 'fishing trip', to understand how well these thiourea and guanidine derivatives could perform as potential anticancer drugs.

A panel of ovarian cancer cells consisting of adherent cell lines EFO-21 and EFO-27 followed by a suspension cell line (COLO-704) were investigated. Parental and cisplatin resistant sublines of these cells were used to observe effects of the thiourea and guanidine derivatives against cisplatin resistance. These cell lines were then dosed with each derivative from the compound library and their biological activity examined through MTT viability. Cisplatin resistant cell lines were the focus due to the broad extent in which the anticancer drug has been researched, but also due to resistant mechanisms it has produced in human cancer cells.

The investigated compounds showed promising results and displayed notable differences in their effects on reducing the viability of ovarian cancer cell lines, with the data collected potentially providing a start to new therapeutic pathways in the battle against cancer resistant cell lines.

Item Type: Thesis (Master of Science by Research (MScRes))
Thesis advisor: Michaelis, Martin
Thesis advisor: Serpell, Christopher
Thesis advisor: Blight, Barry
Uncontrolled keywords: Synthesis Thiourea Guanidine Derivatives Anticancer Overian Cancer MTT Assay Confocal Phosphorescence Iridium Complexes
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 30 Jul 2019 09:20 UTC
Last Modified: 09 Dec 2022 11:50 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/75616 (The current URI for this page, for reference purposes)

University of Kent Author Information

Thomas, Samuel.

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