Design of Biologically Safer Chemicals Based on Retrometabolic Concepts

Abstract

The concept of retrometabolic-based soft drug design and the approaches therewith are reviewed. Several specific examples are given to provide an understanding of the basis for using retrometabolism in the design of safer drugs. Our knowledge of metabolic pathways is now sufficient to predict or evaluate the metabolism of a variety of chemical substances from the point of view of their likelihood of undergoing toxicification or detoxification metabolism. The concept of retrometabolic-based soft drug design needs to be applied to the design of safer commercial chemicals. The rules in transformations applied for designing soft drugs could be extended to the design of soft commercial chemical substances that are less toxic than the existing commercial substances from which they were designed. In doing so, it is quite conceivable that many commercial chemicals currently implicated in environmental and human toxicity could be redesigned and replaced with equally useful but safer substitutes.In the modern era the environment and humans are constantly bombarded by ever increasing number of various manmade chemicals, which are used for a variety of purposes. In the United States, there are over 77,000 chemical substances on the Toxic Substances Control Act list of commercial (industrial) chemical substances. As discussed in Chapter 1, the design, synthesis, and final development of most of these chemicals is strictly useoriented: little or no consideration was (or is) given to designing these