Anticancer and Cytotoxic Properties of Mannich Bases

Abstract

This review outlines the chemistry and anticancer and cytotoxic properties of certain Mannich bases. It is divided into four parts. The first section summarizes briefly various investigations undertaken by other researchers of the chemical and pharmacological properties of a number of Mannich bases against neoplasms. The remaining portions of this review are summaries of work undertaken in this laboratory. The second part presents the following aspects of the anticancer properties of various Mannich bases namely differences in antileukemic activity between certain conjugated styryl ketones and the related Mannich bases, intramolecular cyclization of various acyclic Mannich bases and the effect on anticancer activity of such a process, prodrug approaches with a view to obtaining preferential toxicity to cancerous rather than normal cells and finally the effect on antineoplastic properties of introducing a second basic centre into these compounds. The third section summarizes the promising in vitro activities of different acyclic Mannich bases against the WiDr human colon cancer cells and the preparation of a group of Mannich bases which are effective against certain drug resistant malignant cells. The evidence for and evaluations of a theory proposed by one of the authors called sequential cytotoxicity is presented followed by a description of the very high cytotoxicity of some 4-piperidones; a group of compounds which may be regarded as cyclic Mannich bases. Finally, some biochemical properties of certain of these compounds are outlined especially with reference to their causing inhibition of respiration in mitochondria, particularly in those organelles obtained from neoplastic tissue.