SYNTHESIS OF THIOL -DEPLETING AGENTS WITH SELECTIVE TOXICITY TO MALIGNANT CELLS
| dc.contributor.advisor | Dimmock, J.R. | |
| dc.contributor.committeeMember | Hamon, N.W. | |
| dc.contributor.committeeMember | Hawes, E.M. | |
| dc.contributor.committeeMember | Hindmarsh, K.W. | |
| dc.contributor.committeeMember | Majewski, M. | |
| dc.contributor.committeeMember | Tourigny, G. | |
| dc.creator | Arora, Vinod Kumar | |
| dc.date.accessioned | 2023-12-08T16:34:48Z | |
| dc.date.available | 2023-12-08T16:34:48Z | |
| dc.date.issued | 1991-11 | |
| dc.date.submitted | November 1991 | |
| dc.description.abstract | The present investigation was based on the following two observations. First, derivatives of styryl ketones and their corresponding Mannich bases have been found to possess antineoplastic activity with little or no affinity for the amino or hydroxyl groups found in nucleic acids. In particular the Mannich bases have a pronounced predilection for thiols and react approximately 240 times faster than the corresponding ketones. Hence these compounds may be free from undesired mutagenic and carcinogenic properties associated with present day alkylating agents. Second, L-histidinol which is a structural analog of the essential amino acid histidine has been found to protect normal cells from insult caused by various antineoplastic agents e.g. BCNU(N,N-bis-(2-chloroethyl)-N-nitrosourea), cyclophosphamide, cis-platinum etc.. The aim of the present investigation was twofold and can be oulined as follows. It starts with the synthesis of a vicompound(55a) which contains a Mannich base(a cytotoxic species) and L-histidinol. The Mannich base is a y-piperidone with two arylidene groups attached to the piperidine ring adjacent to the carbonyl function. Second, the design, synthesis and antineoplastic evaluation of some potential alkylating species(A) was contemplated with a view to developing structure-activity relationships and of obtaining a compound with optimum activity. | |
| dc.identifier.uri | https://hdl.handle.net/10388/15324 | |
| dc.subject | Mannich bases | |
| dc.title | SYNTHESIS OF THIOL -DEPLETING AGENTS WITH SELECTIVE TOXICITY TO MALIGNANT CELLS | |
| dc.type.genre | Thesis | |
| thesis.degree.department | Pharmacy | |
| thesis.degree.grantor | University of Saskatchewan | en_US |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |