Can Chemotherapy Be Extended to Include the Intracellular Disease Agents?

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Abstract
The present limits of successful chemotherapy do not quite coincide with the line of division between extracellular and intracellular disease agents. Three investigational approaches are formulated: Direct chemical action on the disease agent; interference with the key-to-lock relationship of virus to susceptible host cell; and rational investiga- tion of cell metabolic systems and their selective inhibition. The 3d approach appears the more promising in that a metabolic inhibitor, or inhibitors, which selectively inhibit a reaction or reactions essential to the intracellular multiplication of the parasite, but unessential to the survival of the host cell may be sought. The Woods-Fildes theory that sulfonamides inhibit an enzyme or enzymes concerned with the anabolism of p-aminobenzoic acid as an essential metabolite, and the Sevag (et al.) theory that sulfonamides act by inhibiting in the susceptible bacteria certain respiratory enzymes which normally mediate reactions yielding the energy essential to bacterial cell division are discussed. It is concluded that the critical sites of chemotherapeutic action are to be found within the system of respiratory enzymes which mediate the aerobic and anaerobic oxidation of glucose and its derivatives. It is suggested that the sulfonamide and the N1 substituted group are capable of combining, respectively, at 2 reaction sites, in appropriate steric relationship, on the enzyme protein. Examples of the inhibition of the enzymatic oxidation of glucose are cited from the literature.