INTERFERENCE WITH BIOLOGICAL PROCESSES THROUGH THE USE OF ANALOGS OF ESSENTIAL METABOLITES

Abstract

This new concept in chemotherapy, first enunciated in 1938, states that a micro- or macro-organism, dependent for its metabolism upon small quantities of any substance, such as a vit., can be killed by somewhat larger quantities of chemically analogous substances. "In some cases the interference can be explained most simply on the basis of a direct competition between the metabolite and its analog for some cellular component for which they both have great affinity; in other cases the data indicate that in addition to competition, other factors operate. Antagonism by related structures may extend to metabolites normally synthesized by the organism whose function is affected." Establishment of this principle of interference with biologic processes through the use of analogs of essential metabolites subtracts some of the empiricism from the purposeful design of new compounds. The types of metabolite antagonism discussed are: sulfonarnides as analogs of p-aminobenzoic acid; nicotinic acid analogs; amino acid analogs and pyrid[image]xine; pantothenic acid analogs; thiamin analog; ascorbic acid analog; analogs of purines and py-rimidines; riboflavin analogs; antagonism of vit. K; antagonism by polyamines.