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PREPARED BY:
DARSHAN R. KANJIYA
11MCY 043
KSKV KACHCHH
UNIVERSITY,
DEPARTMENT OF
CHEMISTRY,
BHUJ
NATURALLY EXTRACTED
DRUGS USED IN MODERN
PHARMACEUTICALS
2
INTRODUCTION TO NATURAL
PRODUCT DRUG DISCOVERY
PROCESS
Natural products are products from
various natural sources, plants,
microbes and animals. Natural
products can be an entire organism(e.g.
a plant, an animal or a micro-
organism), a part of an organism (e.g.
leaves or flowers of a plant, an isolated
animal organ), an extract of an
organism or part of an organism and 3
an exudates, or pure compound (e.g.
alkaloids, coumarins, flavonoids,
lignans, steroids and terpenoids)
isolated from plants, animals or micro-
organisms.
However, in practice, the term natural
product refers to secondary
metabolites, small molecules
(molecular weight < 1500 amu),
produced by an organism, but not
strictly necessary for the survival of the
organism.
4
NATURAL PRODUCTS IN
MEDICINE
The use of natural products, especially
plants, for healing is as ancient and
universal as medicine itself.
The therapeutic use of plants certainly
goes back to the Sumerian and the
Akkadian civilizations in about the
third millenium BC.
Hippocrates, one of the ancient authors
who described medicinal natural
products of plant and animal origins,
listed approximately 400 different
plant species for medicinal purposes.
5
Natural products have been an integral
part of the ancient traditional medicine
systems.
World Health Organization (WHO),
some 3.4 billion people in the
developing world depend on plant
based traditional medicines. This
represents about 88 per cent of the
world’s inhabitants, who rely mainly on
traditional medicine for their primary
health care. 6
Nature has been a potential source of
therapeutic agents for thousands of
years.
An impressive number of modern drugs
have been derived from natural
sources. Over the last century, a
number of top selling drugs have been
developed from natural products.
7
Example :
Anticancer drug Vincristine from Vinca
rosea, narcotic analgesic Morphine
from Papaver somniferum,
antimalarial drug artemisinin from
Artemisia annua, anticancer drug
Taxol from Taxus brevifolia and
antibiotic Penicillins from Penicillium
ssp. are just a few examples.
8
9
DRUG DISCOVERY AND NATURAL
PRODUCT
In modern drug discovery and
development processes, natural
products play an important role at the
early stage of ‘lead’ discovery, i.e.
discovery of the active (determined by
various bioassays) natural molecule,
which itself or its structural analogues
could be an ideal drug candidate.
10
There are at least 2,50,000 species of
higher plants that exist on this planet,
but merely five to 10 per cent of these
terrestrial plants have been
investigated so far.
In addition, re-investigation of
previously investigated plants has
continued to produce new bioactive
compounds that have the potential for
being developed as drugs.
11
 While several biologically
active compounds have
been found in marine
organisms,
e.g. antimicrobial compound
cephalosporin C
from marine organisms
(Cephalosporium,
acremonium
and Streptomyces spp.)
 Antiviral compounds such
as avarol and avarone from
marine sponges.
12
NATURAL PRODUCT DRUG
DISCOVERY
There are two ways of Drug discovery
i). The Traditional way
ii). The Modern processes
13
THE TRADITIONAL WAY
In the traditional, rather more
academic, method of drug discovery
from natural products, drug targets are
exposed to crude extracts, and in the
case of a hit, i.e. any evidence of
activity, the extract is fractionated and
the active compound is isolated and
identified.
Every step of fractionation and
isolation is usually guided by
bioassays, and the process is called
bioassay-guided isolation.
14
The following scheme presents an
overview of a bioassay-guided
traditional natural product drug
discovery process.
Sometimes, a straightforward natural
product isolation route, irrespective of
bioactivity, is also applied, which
results in the isolation of a number of
natural compounds (small compound
library) suitable for undergoing any
bioactivity screening. 15
However, the process can be slow,
inefficient and labor intensive, and it
does not guarantee that a ‘lead’ from
screening would be chemically
workable or even patentable.
16
THE MODERN PROCESSES
Modern drug discovery approaches
involve HTS, where, applying full
automation and robotics, hundreds of
molecules can be screened using
several assays within a short time, and
with very little amounts of compounds.
In order to incorporate natural
products in the modern HTS
programmes, a natural product library
(a collection of dereplicated natural
products) needs to be built.
17
Dereplication is the process by which
one can eliminate recurrence or re-
isolation of same or similar compounds
from various extracts.
A number of hyphenated techniques
are used for Dereplication, e.g. LC-PDA
(liquid chromatography–photo-diode-
array detector),
18
LC-MS (liquid chromatography–mass
detector) and LC-NMR (liquid
chromatography – nuclear magnetic
resonance spectroscopy).
While in the recent past it was
extremely difficult, time consuming
and labor intensive to build such a
library from purified natural products,
with the advent of newer and improved
technologies related to separation,
isolation and identification of natural
products the situation has improved
remarkably.
19
Now, it is possible to build a ‘high
quality’ and ‘chemically diverse’
natural product library that can be
suitable for any modern HTS
programmes.
Natural product libraries can also be of
crude extracts, chromatographic
fractions or semi-purified compounds.
20
However, the best result can be
obtained from a fully identified pure
natural product library as it provides
scientists with the opportunity to
handle the ‘lead’ rapidly for further
developmental work, e.g. total or
partial synthesis, dealing with
formulation factors, in vivo assays and
clinical trials.
21
22
To continue to exploit natural sources
for drug candidates, the focus must be
on exploiting newer approaches for
natural product drug discovery.
These approaches include the
application of genomic tools, seeking
novel sources of organisms from the
environment, new screening
technologies and improved processes of
sample preparation for screening
samples. 23
In addition, the recent focus on the
synthesis of diversity-oriented
combinatorial libraries based on
natural-product-like compounds is an
attempt to enhance the productivity of
synthetic chemical libraries.
24
TYPES OF NATURAL PRODUCTS
According to the sources and
applications of Natural products, it can
be classified as under,
i). Alkaloids
ii). Carbohydrates
iii). Glycosides
iv). Terpenoids
v). Steroids
vi). Phenolics 25

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Naturally extracted drugs used in modern pharmaceuticals.ppt

  • 1. PREPARED BY: DARSHAN R. KANJIYA 11MCY 043 KSKV KACHCHH UNIVERSITY, DEPARTMENT OF CHEMISTRY, BHUJ
  • 2. NATURALLY EXTRACTED DRUGS USED IN MODERN PHARMACEUTICALS 2
  • 3. INTRODUCTION TO NATURAL PRODUCT DRUG DISCOVERY PROCESS Natural products are products from various natural sources, plants, microbes and animals. Natural products can be an entire organism(e.g. a plant, an animal or a micro- organism), a part of an organism (e.g. leaves or flowers of a plant, an isolated animal organ), an extract of an organism or part of an organism and 3
  • 4. an exudates, or pure compound (e.g. alkaloids, coumarins, flavonoids, lignans, steroids and terpenoids) isolated from plants, animals or micro- organisms. However, in practice, the term natural product refers to secondary metabolites, small molecules (molecular weight < 1500 amu), produced by an organism, but not strictly necessary for the survival of the organism. 4
  • 5. NATURAL PRODUCTS IN MEDICINE The use of natural products, especially plants, for healing is as ancient and universal as medicine itself. The therapeutic use of plants certainly goes back to the Sumerian and the Akkadian civilizations in about the third millenium BC. Hippocrates, one of the ancient authors who described medicinal natural products of plant and animal origins, listed approximately 400 different plant species for medicinal purposes. 5
  • 6. Natural products have been an integral part of the ancient traditional medicine systems. World Health Organization (WHO), some 3.4 billion people in the developing world depend on plant based traditional medicines. This represents about 88 per cent of the world’s inhabitants, who rely mainly on traditional medicine for their primary health care. 6
  • 7. Nature has been a potential source of therapeutic agents for thousands of years. An impressive number of modern drugs have been derived from natural sources. Over the last century, a number of top selling drugs have been developed from natural products. 7
  • 8. Example : Anticancer drug Vincristine from Vinca rosea, narcotic analgesic Morphine from Papaver somniferum, antimalarial drug artemisinin from Artemisia annua, anticancer drug Taxol from Taxus brevifolia and antibiotic Penicillins from Penicillium ssp. are just a few examples. 8
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  • 10. DRUG DISCOVERY AND NATURAL PRODUCT In modern drug discovery and development processes, natural products play an important role at the early stage of ‘lead’ discovery, i.e. discovery of the active (determined by various bioassays) natural molecule, which itself or its structural analogues could be an ideal drug candidate. 10
  • 11. There are at least 2,50,000 species of higher plants that exist on this planet, but merely five to 10 per cent of these terrestrial plants have been investigated so far. In addition, re-investigation of previously investigated plants has continued to produce new bioactive compounds that have the potential for being developed as drugs. 11
  • 12.  While several biologically active compounds have been found in marine organisms, e.g. antimicrobial compound cephalosporin C from marine organisms (Cephalosporium, acremonium and Streptomyces spp.)  Antiviral compounds such as avarol and avarone from marine sponges. 12
  • 13. NATURAL PRODUCT DRUG DISCOVERY There are two ways of Drug discovery i). The Traditional way ii). The Modern processes 13
  • 14. THE TRADITIONAL WAY In the traditional, rather more academic, method of drug discovery from natural products, drug targets are exposed to crude extracts, and in the case of a hit, i.e. any evidence of activity, the extract is fractionated and the active compound is isolated and identified. Every step of fractionation and isolation is usually guided by bioassays, and the process is called bioassay-guided isolation. 14
  • 15. The following scheme presents an overview of a bioassay-guided traditional natural product drug discovery process. Sometimes, a straightforward natural product isolation route, irrespective of bioactivity, is also applied, which results in the isolation of a number of natural compounds (small compound library) suitable for undergoing any bioactivity screening. 15
  • 16. However, the process can be slow, inefficient and labor intensive, and it does not guarantee that a ‘lead’ from screening would be chemically workable or even patentable. 16
  • 17. THE MODERN PROCESSES Modern drug discovery approaches involve HTS, where, applying full automation and robotics, hundreds of molecules can be screened using several assays within a short time, and with very little amounts of compounds. In order to incorporate natural products in the modern HTS programmes, a natural product library (a collection of dereplicated natural products) needs to be built. 17
  • 18. Dereplication is the process by which one can eliminate recurrence or re- isolation of same or similar compounds from various extracts. A number of hyphenated techniques are used for Dereplication, e.g. LC-PDA (liquid chromatography–photo-diode- array detector), 18
  • 19. LC-MS (liquid chromatography–mass detector) and LC-NMR (liquid chromatography – nuclear magnetic resonance spectroscopy). While in the recent past it was extremely difficult, time consuming and labor intensive to build such a library from purified natural products, with the advent of newer and improved technologies related to separation, isolation and identification of natural products the situation has improved remarkably. 19
  • 20. Now, it is possible to build a ‘high quality’ and ‘chemically diverse’ natural product library that can be suitable for any modern HTS programmes. Natural product libraries can also be of crude extracts, chromatographic fractions or semi-purified compounds. 20
  • 21. However, the best result can be obtained from a fully identified pure natural product library as it provides scientists with the opportunity to handle the ‘lead’ rapidly for further developmental work, e.g. total or partial synthesis, dealing with formulation factors, in vivo assays and clinical trials. 21
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  • 23. To continue to exploit natural sources for drug candidates, the focus must be on exploiting newer approaches for natural product drug discovery. These approaches include the application of genomic tools, seeking novel sources of organisms from the environment, new screening technologies and improved processes of sample preparation for screening samples. 23
  • 24. In addition, the recent focus on the synthesis of diversity-oriented combinatorial libraries based on natural-product-like compounds is an attempt to enhance the productivity of synthetic chemical libraries. 24
  • 25. TYPES OF NATURAL PRODUCTS According to the sources and applications of Natural products, it can be classified as under, i). Alkaloids ii). Carbohydrates iii). Glycosides iv). Terpenoids v). Steroids vi). Phenolics 25