MANNICH BASES DERIVED FROM STYRYL ALKYL KETONES AND THEIR HYDRAZONE ANALOGS AS POTENTIAL ALKYLATING AGENTS

In the chemotherapy of cancer a number of different classes of drugs are used. Of these, alkylating agents constitute about 30%. Today a few of the less common cancers can be effectively treated by chemotherapy or adjuvant therapy but the majority of the cancers cannot be treated satisfactorily. The drugs that are in clinical use are marked by lack of specificity and high toxicity. Therefore there is a need for effective and selective anticancer drugs. Mannich bases have been found to display a wide range of biological activities. Earlier work from these laboratories have established the potential of some of these compounds as antineoplastic agents. Based on the kinetic and physicochemical considerations resulting from these studies, the synthesis of a number of Mannich bases derived from some conjugated styryl alkyl ketones and their corresponding aryl and aroyl hydrazones have been accomplished and the compounds were evaluated against P388 lymphocytic leukemia in mice. The Mannich bases derived from a series of α,ß-unsaturated ketones I mentioned above can be divided into two series namely, Monoaminomethylated Mannich bases II and Bis-aminomethylated Mannich bases III resectively Of the mono-Mannich bases some of the derivatives with one or more fluorine atoms on the aromatic ring such as the compound IIj(where R1 =F and R2=H) with T/C% of 128, compound IIk(where R1= R2=F) with T/C% of 129 and the compound IIl(where R1=H and R2=F) with T/C% of 120 at dose of 120 mg/kg in each case were found to be active in the P388 prescreen. Of the bis-Mannich bases the compound IIIb (where R1=OCH3, R2=H) was found to be active in the P388 prescreen with a T/C% of 128 at a dose level of 60 mg/kg. These activities were confirmed by repeating the test. During the synthesis of 1-phenyl-1-penten-3-one (Ia, where R1, R2=H) it was found that this starting ketone was contaminated with an isomer i.e. 2-methyl-1-phenyl-1-butene-3-one (Ia to an extent of 10% determined from the proton NMR spectrum

Name thesis:degree_name

Doctor of Philosophy (Ph.D.)

Level thesis:degree_level

Doctoral

Grantor

University of Saskatchewan

Year dc:date.issued

1987

Author dc:creator

• Sastry, Jonnalagadda Seshachalapati

• Mannich bases

Handle dc:identifier.uri

https://hdl.handle.net/10388/15387

OAI identifier oai:identifier

oai:harvest.usask.ca:10388/15387