Medicinal Chemistry

to the tissues of the heart, causing oxygen deprivation and hypoxicdamage to the heart
muscles. Rational drug design for diseases arising from these various endogenous
pathological mechanisms has already been addressed, using the diverse messenger and
nonmessenger design strategies discussed in chapters 4–8.
The remaining two mechanisms of pathology (infectious, toxic) arise primarily from
exogenous pathogens(where a pathogen is any microorganism or other substance caus-
ing disease). These pathogens may be biological (bacteria), chemical (environmental
toxins), or physical (radiation); pathogens may be naturally occurring (viruses) or
human-made (nerve gas). Pathogens may be opportunistic(causing disease only when
the host’s state of health is diminished; e.g., a fungal pneumonia occurring in a person
whose resistance has been lowered by having acquired immune deficiency syndrome
[AIDS]) or indiscriminate(producing disease in any individual, whether healthy or ill,
exposed to the agent; e.g., high levels of radiation).

9.1.1 Types of Exogenous Pathogens

The exogenous pathogens that lead to human disease may be sub-divided into two
broad categories:

1. Microbes
   Prions
   Viruses
   Bacteria
   Fungi
   Parasites


2. Toxins
   Biological
   Chemical
   Physical

Of these two categories of pathogens, microbe-induced infectious diseases are probably
the most important.
The World Health Organization has identified infectious disease as the greatest chal-
lenge to global health. The identification of such an important problem has been made
apparent by the current health crises confronting the modern world. The spectre of AIDS,
SARS (severe acute respiratory syndrome), and West Nile virus emphasizes the looming
importance of infectious disease to the health of our planet. In future years, the summer
months may also be accompanied by increasing problems with malaria in North America
and Europe as global warming heralds fundamental changes to our planet’s ecosystems.
In Africa, bacterial meningitis continues to reach epidemic proportions, with concomitant
increases in polio and tuberculosis.
It is also of great concern that the traditional antibiotic drugs (the miracle agents of
the 20th century) are becoming increasingly ineffective against an ever-enlarging
number of bacteria. In the United States, a recent National Academy of Science report
identified resistance to conventional antibiotics and the need for new antibiotics as cru-
cial issues. The “To Market, To Market” summaries of the Annual Reports in Medicinal

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