Synthesis and Evaluation of Benzoyl containing compounds as potential anti-cancer agents

Ahmed, Saqib Munir

Abstract

Seen as one of the major causes of death worldwide, Cancer requires the development of effective treatments to combat the disease. However, pharmaceutical companies are faced by the challenge of finding and developing a suitable compound that can override the barriers of the human body and operate effectively in its pharmacological properties.
This thesis and the research look at a naturally occurring compound, Dibenzoyl methane (DBM), its derivatives, and a few additional synthesised compounds with similar chemical properties and their unique activities demonstrated. DBM and its derivatives are classified as β-diketones and were synthesised using two different chemical schemes; the Baker-Venkataraman rearrangement and the Claisen acylation.
In comparison to this, a recently discovered synthetic class of compounds, N-benzoyl-N’-phenylurea and derivatives were also studied during the period of this investigation. The cytotoxicity of the drug candidates was determined on live mammalian cell lines including HepG2, HeLa and HCT 116 amongst a few supplementary cell lines using the MTT assay. Furthermore, as the final stage of a potential drug compound is associated with different mechanisms of the human body such as A.D.M.E, pharmacological factors such as stability within plasma and metabolic stability were measured. These are responsible for measuring the degradation of the compound over time and looking at the ability of the liver to remove the administered drug respectively. In addition, proceedings of the investigation led to quantitative real time PCR (qPCR) being conducted to analyse levels of gene expression. Observations were made with regards to gene expression on the cyclin-dependent kinase family which are involved in processes such as cell division and differentiation The data was collected, plotted, and analysed to assess the efficacy of the drug candidates as potential anti-cancer agents.
It was found that several of the synthesised compounds exerted better activity than others, with DBM and compounds containing the O-H hydroxyl group performing better in screening for stability and toxicity. In addition, it was seen that the bulkier compounds, such as the -benzoyl-N’-phenylurea derivatives performed better in the assay for plasma stability. Therefore, it can be hypothesised that increasing the size of a compound to make it bulky can in turn improve pharmacological factors however the presence of different functional groups can lead to better toxicity and stability, thus when designing or synthesizing a compound, the approach of using heavier compounds, with many functional groups should be considered.

Citation

Ahmed, S. M. Synthesis and Evaluation of Benzoyl containing compounds as potential anti-cancer agents. (Thesis). University of Salford

• Thesis Type: Thesis
• Deposit Date: Apr 12, 2022
• Publicly Available Date: May 12, 2022
• Award Date: Mar 31, 2021