CYTOTOXIC EVALUATION OF SOME MANNICH BASES OF CONJUGATED STYRYL KETONES
Cancer chemotherapy provides a very effective means of cancer treatment. The major disadvantage of using antineoplastic agents is their lack of selective toxicity between normal and malignant cells. In addition, over a long period of time, carcinogenicity, mutagenicity and resistance may develop. These problems necessitate the development of new anticancer drugs which could target biomolecules other than nucleic acids and which should have different chemical available medication. To seek to overcome the structures than the currently problems associated with clinically used antineoplastic agents, the following study was undertaken. The main objective of the present work was to design cytotoxic agents which should be highly potent and should display high preference towards cancerous cells. In order to achieve these aims, a series of compounds containing the a, (3-unsaturated ketone moiety were taken as lead molecules. The rationale for selecting the enone function as a pharmacophoric group for the development of anticancer agents was its preferential electrophilicity for thiols in contrast to amino or hydroxy groups. Hence such compounds will have relatively little tendency to attack nucleic acids which have no thiol groups. Therefore such compounds may be devoid of carcinogenicity and mutagenicity. Earlier studies have demonstrated that ivcertain a,0-unsaturated ketones when evaluated for their action in the murine P388 leukemia screen, were devoid of antineoplastic activity. However their corresponding Mannich bases resulted in several analogs with antineoplastic activity and increased avidity for thiols compared to their precursors. Several analogs of Mannich bases were designed on the basis of some of the established approaches in rational drug designing.
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