TOPIC I

INTRODUCTION
•EARLY MEDICINAL USE
•HOW PHARMACOLOGICALLY ACTIVE COMPOUNDS WERE
IDENTIFIED: THE BEGINNING OF THE PHARMACEUTICAL
INDUSTRY
•THE STAGES OF DRUG DISCOVERY AND DEVELOPMENT IN
MODERN TIMES
 EARLY MEDICINAL USE
 Early writings on papyrus and clay tablets describe many kinds of disease, and list a wide variety of herbal
and other remedies used to treat them.
The earliest such document, the famous Ebers papyrus, dating from around 1550BC, describes more than
800 such remedies
Evidence for ‘disease and its management’ in the pre historic period is limited to
• fossilized bony lesions
• Comparing with Aborigines
• Cave Drawings
• Predators
GREEK MEDICINE
MEDICINE IN 17th & 18th CENTURY
 MEDICINE IN 18th CENTURY
 The Scratch that Saved a Million Lives: The Discovery of Vaccines
Edward Jenner, Pupil of John Hunter, invented the worlds first vaccine for small pox in 1789. Jenner
inoculating James Phipps with cowpox, a virus similar to smallpox, to create immunity to SMALL POX.
 Even in the 18th century the search for a simple way of healing the sick continued. Jenner is said to have
saved more lives than the work of any other human being.
 PHRENOLOGY : Propounded by Franz Joseph Gall, Contours of the skull is a guide to an individual’s
mentality and character traits.
 Mesmerism : A belief in “animal magnetism” sponsored by Franz Anton Mesmer,
 Samuel Hahnemann : • The originator of homeopathy • Treatment Involves administration of minute doses
of drugs
 The structure of the human body was almost fully known, due to new methods of microscopy and of
injections. Even the body’s microscopic structure was understood.
 MEDICINE IN 19th CENTURY
 Johannes Müller- Established Physiology as a distinct science
 Claude Bernard : •carefully planned experiments • Role of pancreas in digestion, •Presence of
glycogen in the liver, •vasomotor nerves
 French chemist Louis Pasteur : established the science of bacteriology •Discovered Rabies Vaccine
 •In 1870s, developed practical applications of the germ theory of disease. •use of carbolic acid
(Phenol) as an antiseptic
 Another Pioneer Robert Koch, showed how bacteria could be cultivated, isolated, and examined •
discovered M. tuberculosis, in 1882, and Vibrio Cholera
 1846 – William. T. G. Morton, • For the Relief of Unbearable Pain: Discovery and use of Ether during
Surgery
How pharmacologically active compounds were identified: the beginning of the pharmaceutical
industry

Examples of pharmacologically active substances derived from plants include

 morphine from opium poppy,

nicotine from the tobacco plant,

 cannabinoids from cannabis leaves,

caffeine from tea and coffee,

cardiac glycosides (digoxin and digitoxin) from woolly foxglove,

quinine from the cinchona tree,

and salicylates from the bark of the white willow tree

 Morphine was the first plant alkaloid isolated in a pure state by a 23-year-old apothecary named Friedrich
Willhelm Serturner (1783–1841)
 When available in a pure form, the pharmacological activity and toxicity of these alkaloids increased
considerably and many were deadly poison
 By the mid-1800s, German scientists began to dominate the field of analytical and organic chemistry, with
such luminaries as Friedrich Wohler (1800–1882), famed for the synthesis of urea ¨ ‘without the help of a
kidney’ simply by heating ammonium cyanate
 The subject of pharmacology (Materia Medica) was established as a scientific discipline in the latter half of
the nineteenth century by people such as Rudolf Buchheim (1820–1879), Oswald Schmiedeberg (1838–1921),
Paul Ehrlich (1854–1915), and Henry Dale (1875–1968)
 The doyen among German organic chemists during much of the nineteenth century discovered the volatile
liquid chloroform (CHCl3)
 The first synthetic drugs and, indeed, the entire pharmaceutical industry can be traced to the manufacture of
textiles and synthetic dyes, as exemplified by mauveine (mauve), which was discovered by a young British
chemist William Henry Perkin (1838–1907)
 One of the first German chemical firms to show an interest in pharmaceuticals was the Friedrich Bayer
Company, founded in 1863, and originally located in Barmen, Germany (today in Leverkusen)

 An example of one of the many aromatic compounds derived from coal-tar was naphthalene, which was
used as an intestinal antiseptic for, among other things, the irradiation of worms.

When a patient with this condition who also happened to be suffering from a fever received naphthalene,
the fever was cured but not the worms.

On closer inspection it turned out that the pharmacist had made a mistake and instead of naphthalene,
another derivative of coal-tar, acetanilide had been prescribed.

This led the Bayer Company to develop and market acetanilide as the first synthetic antipyretic drug,
which became known commercially as Antifebrin (fever-reducing)

 In 1887, the Bayer Company began to manufacture phenacetin which eventually became more successful
as an analgesic-antipyretic agent than acetanilide
 In the 1950s, a small US drug firm, McNeil laboratories, began to develop N-acetyl-p-aminophenol as a new pharmaceutical
product, named Tylenol Elixir.

 This liquid formulation was especially suitable for children and the elderly and was approved for this purpose by the Food and Drug
Administration (FDA) in 1955.

Tylenol was also manufactured in tablet form (500 mg), becoming a blockbuster drug available over-the-counter

Aspirin was marketed as a highly successful pharmaceutical product by the Bayer Company in 1897

 after hydrolysis and oxidation gives salicylic acid. The first well-documented clinical trial of salicylates in medicine is credited to
an English clergyman, the Reverend Edward Stone (1702–1768)

 Willow-bark extracts had been used with great benefit in the treatment of a host of medical complaints, including aches and pains,
fevers and chills.

 In 1853, a French chemist Charles Frederic Gerhardt (1816–1856) heated an extract of willow bark with acetyl chloride and in this
reaction he succeeded in producing, for the first time, acetylsalicylic acid
 MODERN APPROACHES IN DRUG
DISCOVERY FROM NATURAL PRODUCTS
Natural product extracts frequently contain a large number of constituents comprising those, which are difficult to
separate.

The unambiguous structures of pure compounds can be determined by the combination of conventional techniques
like ultraviolet absorption spectroscopy (UV), IR, MS and NMR

One of the new technologies in drug discovery from natural products is the use of capillary electrophoresis (CE)
screening program first developed by Cetek Corporation and Cubist.

The assay is able to identify active natural product compounds/ extracts and by detecting any shift in the protein
when a ligand binds to it due to the conformational and surface charge changes.
The natural products and related drugs exhibit a broad spectrum of pharmacological activities, and

they are used for the treatment and/or prevention of most of the popular human diseases, including infectious

diseases, cancers, peptic ulcers, as immuno modulators, anticoagulants, antioxidants, respiratory,

digestive and cardiovascular system-related diseases, antidiabetics, etc

About 35% of the annual global market of medicine is either from natural products or related drugs; mainly
including plants (25%) followed by microorganisms (13%) and animal(3%) sources

The new chemical entities (NCEs) can be discovered from one of the four major natural sources including
plants, marine, animals, and microorganisms (fungi and bacteria).

In addition to these natural sources, the new compounds can also be prepared by using synthetic chemistry and
combinatorial chemistry.

1. Selection of Plants for Screening Based on Ethnopharmacological Knowledge, random approach and
approach Based on Traditional System of Medicine
2. Authentication of the collected raw materials is the basic starting point in the development of natural
products. The authentication of plant materials may be achieved through the application of one or more of the
methods involving taxonomic, macroscopic, microscopic, chromatographic, spectroscopic, chemometric,
immunoassays, and DNA fingerprinting analysis.
3. Extraction and Isolation of Natural Compounds Using Biological-Activity Guided Fractionation.
The fractionation of extract is based on biological activity rather than a class of compound of interest which
involves step-by-step separation of the plant extract. On the basis of physicochemical properties and
screening for biological activity, further fractionation and screening are followed.
The chemical characterization and structural elucidation are performed after the identification of the active
isolates.
A. extraction
B. Fractionation
C. Isolation and Purification
 References
1. Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their
Analogues as Potential Therapeutic Agents. Available from:
https://www.researchgate.net/publication/357651462_Modern_Approaches_in_the_Discovery_and_Develop
ment_of_PlantBased_Natural_Products_and_Their_Analogues_as_Potential_Therapeutic_Agents
2. Chapter 1 in Hill, R. G. and Rang, H. P Drug discovery and development – technology in transition,
Churchill Livingstone Elsevier; 2nd ed. (August 30, 2012), Paperback ISBN: 9780702042997, eBook
ISBN: 9780702053160
3. Jantan, I., Bukhari, S.N.A., Mohamed, M.A.S., Wai, L.K. & Mesaik, M.A (2015). Chapter 1. In: Drug
Discovery and Development – From Molecules to Medicine. Intech Open. http://dx.doi.org/10.5772/59603