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.