Use this URL to cite or link to this record in EThOS:
Title: Mechanistic studies on aziridinylbenzoquinones and CCNU [l-(2-chloroethyl)- 3-cyclohexyl-l-nitrosourea] in cultured tumour cells
Author: Ben Raba, Fatma Mohammed
ISNI:       0000 0001 3457 1133
Awarding Body: University of Salford
Current Institution: University of Salford
Date of Award: 2007
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Thesis embargoed until 31 Jul 2022
Access from Institution:
This work is concerned with the action of two different anticancer drugs which can alkylate DNA in tumour cells. The first alkylating agent studied was CCNU [(l-(2-chloroethyl)-3-cyclohexyl-lnitrosourea, Lomustine]. This is a well established clinically used lipophilic anticancer drug. This drug crosses the blood brain barrier and is used routinely for the treatment of certain types of brain tumours, in particular in childhood malignancies e.g. (cerebellar astrocytoma, Medulloblastoma). HPLC studies showed that CCNU and its common metabolites have very high partition coefficients and are unstable in aqueous solutions. Cytotoxicity studies showed that both parent compound and metabolites are equitoxic against a number of leukaemic cell lines (K562, Molt-4, Nalm-6 and Jurkat) and a tumour cell line derived from the central nervous system (Daoy). Flow cytometry studies showed that the compounds cause cells to arrest in the G2-M phase of the cell cycle and can also induce apoptosis. The second alkylating agent studied was RH1 (2, 5-diaziridinyl-3 -hydroxymethyl-6- methyl-1, 4-benzoquinone) which is a novel water soluble prodrug which is currently undergoing clinical trials. The activity of RH1 was compared with a new lipophilic ester derivative of RH1, Es5. It was found using HPLC, Cytotoxicity, comet and flow cytometry studies that these two quinones behave very similarly in that their cell killing potencies are enhanced by the presence of the reducing enzyme DT-Diaphorase in the cells. However we have shown that Es5 has a much higher partition coefficient than RH1 and yet following cleavage of the ester group produces a quinone whose Cytotoxicity profile is very similar to RH1. The possibility of using Es5 as an alternative drug to CCNU is discussed.
Supervisor: Not available Sponsor: Minisitry of Higher Education in Libya ; Libyan Embassy in London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available