Drug Design- Methodology, Concepts, and Mode-of-Action

Drug Design- Methodology, Concepts, and Mode-of-Action

The targeted route to medicines is an old dream of humanity. Even the alchemists
sought after the Elixir, the Arcanum that was meant to heal all disease. It still has
not been found today. On the contrary, drug therapy has become even more
complicated as our knowledge of the different disease etiologies has become
more complex.
Nonetheless, the success of drug research is impressive. For hundreds of years,
alcohol, opium, and solanaceae alkaloids (from thorn apples) were the only preparatory
measures for surgery. Today general anesthesia, neuroleptanalgesia, and
local anesthetics allow absolutely pain-free surgical and dental procedures to be
carried out. Until this century, plagues and infectious diseases have killed more
people than all wars. Today, thanks to hygiene, vaccines, chemotherapeutics, and
antibiotics, these diseases have been suppressed, at least in industrialized countries.
The dangerously increasing numbers of therapy-resistant bacterial and viral pathogens
(e.g., tuberculosis) have presented new problems and make the development
of new medications urgently necessary. The H2-receptor inhibitors and protonpump
inhibitors have drastically reduced the number of surgical procedures to treat
gastric and duodenal ulcers. Combinations of these inhibitors with antibiotics have
brought even more advances in that it allows a causal therapy (▶Sect. 3.5).
Cardiovascular diseases, diabetes, and psychiatric diseases (diseases of the central
nervous system, CNS) are treated mostly symptomatically, that is, the cause of the
disease is not addressed, but rather the negative effects of the disease on the
organism. Often the therapy is limited to slowing the progression of these diseases
or increasing the quality of life. Synthetic corticosteroids have lead to significant
pain reduction and retardation of the pathological bone degeneration associated
with chronic inflammatory diseases (e.g., rheumatoid and chronic polyarthritis).
The spectrum of cancer therapy ranges from healing, particularly in combination
with surgical and radiation therapy, all the way to complete failure of all therapeutic
measures.
The history of drug research can be divided into several sequential phases:
• the beginning, when empirical methods were the only source of new medicines,
• targeted isolation of active compounds from plants,
G. Klebe, Drug Design, DOI 10.1007/978-3-642-17907-5_1,