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Role of natural product in drug discovery
Citation preview
WELCOME
ROLE OF NATURAL
PRODUCTS IN NEW DRUG
DEVELOPMENT
presented by:
RAHUL B S
M Pharm
Pharmaceutical Chemistry
CONTENTS
INTRODUCTION
DRUG DEVELOPMENT
NATURAL PRODUCTS
ROLE OF NATURAL PRODUCTS IN DRUG DEVELOPMENT
CLSSIFICATION OF NATURAL PRODUCTS
CONCLUSION
REFERENCE
Take years to decade for discovering a new drug and very costly
It involves
INTRODUCTION
Choose a disease
Choosing drug target
Identifying bio assay
Finding lead compound
Isolation and purification Isolation and purification
Find
Structural determination
Herbal medicine
CHOOSING A DISEASE
Pharmaceutical companies
will also avoid products that
would be consumed by
individuals of lower economic
status (i.e. a disease which only
affects third world countries).
Pharmaceutical companies have to consider
economic factors as well as medical ones. A huge
investment has to be made towards the research and
development of a new drug. Therefore the companies
must ensure their financial return.
Most research is carried out on diseases which
afflict “first world” countries: (e.g. cancer, cardiovascular
diseases, depression, diabetes, flu, migraine, obesity).
IDENTIFYING A DRUG TARGET
Drug Target is a specific macromolecule, or biological
system, which the drug will interacts.
Identification of drug targets allows researchers to identify
whether agonist or antagonist should be designed for a particular
receptors.
Eg; agonist of serotonin receptor are use for treating migraine and
antagonist of dopamine receptor are useful as antidipressants
CHOOSING THE BIOASSAY
Definitions:
In vitro: In an artificial environment, as
in a test tube or culture media
In vivo: In the living body, referring to
tests conducted in living animals
Ex vivo: Usually refers to doing the test
on a tissue taken from a living organism.
FINDING THE LEAD
Screening Natural Products
Screening synthetic banks
Existing drugs
Enhancing a side effect
Starting from a natural ligand and or modulator
Combinatorial / parallel synthesis
Computer aided design of lead compound
Serendipity
Fragment based lead discovery
ISOLATION AND PURIFICATION
If the lead compound is present in a mixture of compounds,
obtained from natural / synthetic source should be isolated and
purified.
STRUCTURAL DETERMINATION
This can be done by various spectral data obtained by using NMR,
IR, X ray crystallography etc.
HERBAL MEDICINE
Drugs or lead compound can be isolated from natural source.
DRUG DEVELOPMENT
The process of bringing a new drug to the market, once a
lead compound has been identified through the process of drug
discovery.
NATURAL PRODUCTS
Natural products are the richest source of biologically active
compounds.
Many today's medicines are either obtained directly from
natural source or were developed from a lead compound originally
obtained from a natural source.
ROLE OF NATURAL PRODUCTS IN DRUG
DEVELOPMENT
The natural products can be classify into
PLANT SOURCE
Most of biological active natural products are plant secondary
metabolites with complex structures.
Plants are consider as one of the richest source of lead
compounds
Eg;
MORPHINE - PAPAVER SOMNIFERUN
COCAINE - ERYTHROXYLUM COCA
DIGOXIN - DIGITALIS
QUININE - CINCHONA
Morphine from Papaver Somniferun
Quinine from Cinchona
Quinine, Cinchona officinalis, Rubiaceae Calisaya type
Digitalis, Digitalis purpurea (Scrophulariaceae)Common name: Fox glove
Animal sources
Animals can sometimes be a source of new
pharmacologically active nature products.
For example,
A series of antibiotic peptides were extracted from the
skin of the African clawed frog and a potent analgesic compound
called epibatidine was obtained from the skin extracts of
the Ecuadorian poison frog.
EPIBATIDINE
Epibatidine is an alkaloid originally extracted in the 1970s from the
skin secretions of a tiny poison frog from Ecuador.
Today it is a major research tool in the development of analgesics, and
several epibatidine derivatives are promising drug leads.
Microorganisms
Microorganisms are another potent source of drug leads.
The classic example of such a drug discovery is the that of
penicillin by Alexander Fleming.
Marine sources
In recent years, there has been a great interest in finding
pharmacologically active nature products from marine sources.
Coral, sponges, fish, and marine microorganisms have a
wealth of biologically potent chemicals with interesting
inflammatory, antiviral, and anticancer activity.
For example, curacin A is obtained from a marine
cyanobacterium and shows potent antitumor activity.
Other antitumor agents derived from marine sources include
eleutherobin, discodermolide, bryostatins, dolostatins, and
cephalostatins.
curacin
VENOM AND TOXINS
Venom and toxins from animals, plants, snake, spiders,
scorpions, insects and micro organisms are extremely potent, since
they have very specific interactions with a macromolecular target in
the body.
Venom and toxins have been used as lead compounds in the
drug development of novel drugs.
Brazilian viper
Captopril
Teprotide
Eg: Teprotide a peptide isolated from the venom of Brazilian viper, was
a lead compound for the development of the antihypertension
agent captopril.
Conclusion
Natural products and their derivatives have historically been invaluable
as a source of therapeutic agents.
In the past decade, research into natural products in the pharmaceutical
industry has declined, owing to issues such as the lack of compatibility of
traditional natural-product extract libraries with high-throughput screening.
Recent technological advances that help to address these issues,
coupled with unrealized expectations from current lead-generation strategies,
have led to a renewed interest in natural products in drug discovery.
Various screening approaches are being developed to improve the
ease with which natural products can be used in drug discovery campaigns,
and data mining and virtual screening techniques are also being applied to
databases of natural products. It is hoped that the more efficient and effective
application of natural products will improve the drug discovery process.
Reference
Patrick GL. An introduction to medicinal chemistry, 4th ed. Oxford University Press;
2009. p. 187-91, 377- 407
Vincent P. Gullo Æ James McAlpine Æ Kin S. Lam Dwight Baker Æ Frank Petersen.
Drug discovery from natural products. J Ind Microbiol Biotechnol (2006) 33: 523–531.
http://amphibianrescue.org/tag/epibatidine/.
Klaus Angerer. Frog tales on poison dart frogs, epibatidine, and the sharing of
Biodiversity. The European Journal of Social Science Research Vol. 24, No. 3, September
2011, 353369.
Alan L. Harvey. Natural products in drug discovery. Drug Discovery Today Volume
13, Issues 19–20, October 2008, Pages 894–901.
All data were collected from various sources , only for academic purposes.