SYNTHESIS, ANTINEOPLASTIC EVALUATION AND KINETIC STUDIES OF SOME MANNICH BASES
| dc.creator | Shyam, Krishnamurthy | |
| dc.date.accessioned | 2024-01-16T17:32:25Z | |
| dc.date.available | 2024-01-16T17:32:25Z | |
| dc.date.issued | 1982 | |
| dc.date.submitted | 1982 | |
| dc.description.abstract | Mannich bases have been found to display a wide range of biological activities. However, there is a paucity of information in the literature regarding the anticancer properties of these compounds. Therefore three different types of Mannich bases, viz., those derived from (a) aceto-phenones, (b) benzalacetones and (c) 1-phenyl-l-nonen-3-one were prepared and were evaluated against P388 lymphocytic leukemia in mice. The Mannich bases derived from acetophenones could be broadly divided into three groups: (i) 3-amino-1-aryl-1-propanone hydrobromides, (ii) 3-amino-l-aryl-l-propanone -methobromides and (iii) 3-amino-2-aminomethyL-1-aryl-l-propanones. Of these compounds, while (i) and (ii) were uniformly inactive against P388 lymphocytic leukemia, (iii) showed variable and sometimes, appreciable activity. Repre-sentative compounds from (i) and (iii) were also screened for respiration-inhibitory activity in rat liver mitochondria. It was found that (iii) were approximately one hundred times more active than .(1). A Topliss analysis of the results obtained in the case of (iii) revealed a -a dependency for activity in the P388 screen and a +a dependency for respira-tion-inhibitory activity in rat liver mitochondria. An attempt was then made to explain the anticancer activities found in the cases of (i), (ii) and (iii) in terms of the susceptibility of each series of compounds to (3-elimination whereby acrylophenones were generated which could act as alkylating agents. Stability studies and kinetic experiments were carried out to achieve this objective and revealed that under the experimental conditions utilised while no sign of 13-elimination was discerned in the case of (i), (ii) under-went extremely rapid elimination to generate the correspond-ing acrylophenones at pH 7.4. Since both (i) and (ii) were inactive against P388 lymphocytic leukemia, the appreciable activity displayed by some members of (iii) was explained in terms of optimal rates of breakdown of the parent compounds to generate the alkylating species. One compound belonging to this series, viz., 3-dimethylamino-2-dimethylaminomethyl-1- (4-methoxyphenyl) -1-propanone dihydrochloride was designated a selected agent compound by the National Cancer Institute, U.S.A. and was screened against a number of other tumours. | |
| dc.identifier.uri | https://hdl.handle.net/10388/15437 | |
| dc.subject | Mannich bases | |
| dc.title | SYNTHESIS, ANTINEOPLASTIC EVALUATION AND KINETIC STUDIES OF SOME MANNICH BASES | |
| 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.) |