Medicinal Chemistry

Bacteria

Fungi

Parasites

b. Environmental toxins

Biological

Chemical

Organic

Inorganic

Physical

Within each of these categories there is a further refinement of targets. As discussed
in chapter 9, for example, possible druggable targets for antifungal drug design may be
subdivided as follows:

1. Fungal membrane disruptors via mechanical insertion


2. Ergosterol biosynthesis inhibitors via 14α-demethylase enzyme inhibition


3. Ergosterol biosynthesis inhibitors via squalene epoxidase enzyme inhibition


4. Ergosterol biosynthesis inhibitors via ∆^14 -reductase enzyme inhibition


5. Fungal cell wall disruptors

These subclassifications are given in detail in the corresponding chapters (4–9). (As
an extension to the MANMETS system, the authors devised a further classification
system based entirely on molecular structure. Drug molecules were divided into acyclic
and cyclic structures, which were then further subdivided. For example, the cyclic mol-
ecules were categorized into steroids, heterocycles, and so on. These were then subcat-
egorized; for instance, heterocycles had many subcategories including benzodiazepines,
imidazolidinediones, dihydropyridines, etc. Regrettably, this classification system is too
extensive and too cumbersome to be useful. Furthermore, the connection to biological
intuition is lost in such a system. Accordingly, it will not be presented in this book.)
The MANMETS system is a “bottom-up” classification system. It starts at the level
of the biomolecule and works up to the pathological processes (traumatic, toxic, ...),
then to the physiological systems (cardiovascular, endocrine, ...) and ultimately to the
diseases affecting these systems. Because of its molecular-based approach, it offers def-
inite advantages for drug design. MANMETS classifies the molecular targets that are
biochemically relevant to human disease and to drug design.
The goal of medicinal chemistry is to design novel chemical compounds that will
favorably influence ongoing biochemistry in the host organism in some beneficial manner.
As discussed in chapters 4–6, one of the most obvious approaches is to either mimic or
block endogenous messengers used by the organism itself to control or alter its own bio-
chemistry. These endogenous messengers may be neurotransmitters (fast messengers),
hormones (intermediate), or immunomodulators (slow), working at the electrical, mole-
cular, or cellular levels, respectively. However, not all pathologies that afflict the human
organism can be addressed by manipulation of these messengers. Accordingly, it becomes
necessary to directly target other cellular components and/or endogenous macromolecules
that are not normally directly controlled through binding to endogenous messengers.

190 MEDICINAL CHEMISTRY