SYNTHESIS OF a,ß-UNSATURATED-1,3-DIKETONES AND RELATED MANNICH BASES FOR EVALUATION AGAINST VARIOUS NEOPLASMS

In the chemical warfare against cancer, different classes of drugs are employed. However, since a majority of these drugs have been developed with a common target in mind, namely DNA, they have the potential of being carcinogenic and mutagenic. In addition they are associated with host toxicity and drug resistance. Hence, there is a need for new anticancer drugs especially those which have greater toxicity for neoplasms than normal tissues. Mannich bases have been found to display a wide range of biological activities. Earlier workers from these laboratories have established the potentiality of some of these compounds as antineoplastic agents. Based on kinetic and physicochemical considerations resulting from these studies, the synthesis of a number of Mannich bases derived from some substituted 3-arylmethylene-, 3- heteroarylmethylene- and 3-aralkenylmethylene diketones has been accomplished and the compounds were evaluated against P388 lymphocytic leukemia in mice. The Mannich bases derived from the 1,3-diketones mentioned above could be divided into two groups, namely (1) monoaminomethylated Mannich bases and (2) bisaminomethylated Mannich bases. Of these compounds, while (2), with the exception of the cinnamylidene derivative, were uniformly inactive against P388 lymphocytic leukemia in an in vivo screen, some representative compounds from (2), viz., bis Mannich bases of p-hydroxy and p-methoxy benzylidene diketones, were active in the in vitro screen against a number of tumour systems. These two compounds were designated Selected Agent Compounds by the National Cancer Institute, USA, and were screened or are in the process of being screened against a number of other tumours in vivo. Compounds belonging to (1) showed variable and sometimes, appreciable activity. Two compounds belonging to series (1), viz., the 3,4-dichloro and the terephthalidene analogs were designated Selected Agent Compounds by the National Cancer Instiute, USA, and were screened or are being screened against a number of other tumours in mice.

Name thesis:degree_name

Doctor of Philosophy (Ph.D.)

Level thesis:degree_level

Doctoral

Grantor

University of Saskatchewan

Year dc:date.issued

1984

Author dc:creator

• Raghavan, Srinivas Krishnaswamy

Committee member dc:contributor.committeemember

• Locock, R.A.

• new anticancer drugs
• Mannich bases

Handle dc:identifier.uri

https://hdl.handle.net/10388/15275

OAI identifier oai:identifier

oai:harvest.usask.ca:10388/15275