Medicinal Chemistry

territory. Several research institutes and well-established groups (notably the Scripps
Institute of Oceanography and the University of Hawaii) are producing some very promis-
ing results in this field. The isolation of prostaglandins from a coral was one of the more
startling recent discoveries in marine pharmacology. Figure 3.2 shows how a plant can
be “treated” for medicinal extracts.
An extension of natural products chemistry is the biochemical information derived
from the study of metabolic pathways, enzyme mechanisms, and cell physiological
phenomena; this research has revealed exploitable differences between host and para-
site (including malignant cells), and between normal and pathological function in terms
of these parameters. The large and fertile area of antimetabolite(metabolic inhibitors)
andparametabolite(metabolic substitutes) chemistry is based on such stratagems, and
has found use in the field of enzyme inhibition and in conjunction with nucleic acid
metabolism. The design of drugs based on biochemical leads remains a highly sophis-
ticated endeavor, light-years removed from the random screening of sulfonamide dyes
in which it has its origin.

3.2.5 Lead Compound Identification by Rational Drug Design

The previous two methods of lead compound discovery exploited naturally occurring
endogenous or exogenous compounds. However, of the approximately 10^200 “small”
organic molecules that could theoretically exist in our world (10^52 of which are drug-
like molecules), many would be purely synthetic substances that do not occur naturally.
The lead compound discovery methods discussed in sections 3.2.5 and 3.2.6 afford an

DESIGNING DRUG MOLECULES TO FIT RECEPTORS 117

Figure 3.2 Drugs from natural sources: different molecules can be isolated from the leaves,
stems, and roots. From each of these sources, extracts conducted with solvents with different polar-
ities will yield different natural products. This complex extraction system ensures the identifica-
tion of all possible candidate molecules from a plant source.