Biomedical Engineering Reference
In-Depth Information
CH
3
HO
H
N
H
H
OH
OH
N
O
H
O
O
N
CH
3
O
HO
N
Morphine
Hyoscyamine
Quinine
O
O
H
HO
H
H
O
H
OH
O
O
3
H
H
Digitoxin
FIGURE I.1
Chemical structures of four naturally occurring classical therapeutic agents.
pathology, and computer technologies play important roles. The key research objective of medicinal
chemistry is to investigate relationships between chemical structure and biological effects. When
the chemical structure of a particular drug candidate has been optimized to interact with the bio-
logical target, the compound further has to fuli ll a multifaceted set of criteria before it can be safely
administered to patients. Absorption-distribution-metabolism-excretion (ADME) and toxicology
studies in animals and humans are time-consuming research tasks, which often call for redesign of
the chemical structure of the potential therapeutic agent investigated. It is an iterative process that
is bound to end up in an overall compromise.
I.2 DRUG DISCOVERY—A HISTORICAL PERSPECTIVE
In early times, there was no possibility of understanding the biological origin of a disease. Of neces-
sity, progress in combating disease was disjointed and empirical. The use of opium, ephedra, mari-
juana, alcohol, salicylic acid, digitalis, coca, quinine, and a host of others still in use, long predates
the rise of modern medicine. These natural products are surely not biosynthesized by plants for our
therapeutic convenience; we believe they have survival value to the plants in dealing with their own
ecological challenges.
The presence of biologically active substances in nature, notably in certain plants, was in medi-
eval times interpreted more teleologically. In the early sixteenth century, the German medical doc-
tor and natural scientist, Paracelsus, whose birth given name was Phillip von Hohenheim but later
changed to Philippus Theophrastus Aureolus Bombastus von Hohenheim, formulated the “Doctrine
of Signatures:”
Just as woman can be recognized and appraised on the basis of their shape; drugs can easily be identi-
i ed by appearance. God has created all diseases, and he also has created an agent or a drug for every
disease. They can be found everywhere in nature, because nature is the universal pharmacy. God is the
highest ranking pharmacist.
The formulation of this doctrine was in perfect agreement with the dominating philosophies at that
time, and it had a major impact on the use of natural medicines. Even today, remanences of this
