drug discovery,process,history,HTS,approval\

1. HERBS AS A MAJOR
SOURCE OF DRUG
DISCOVERY
Presented by:
Kale Mayuri
pg no 1NDMVP college of pharmacy, Nashik.
Guided by:
Dr. A.N. Aher
(HOD, Department of
pharmacognosy)

2. INTRODUCTION
Natural products including plants animals and
minerals have been the basis of treatment of human
diseases.
 Neverthless, ancient wisdom has been the basis of
modern medicine and will remain as one important
source of future medicine and therapeutics.
History of medicine dates back practically to the
exixtence of human civilization, Historically the
majority of new drugs have been generated from
natural products(secondary metabolites) and from
the compounds derived from natural products.
pg no 2

3. SOURCESOFDRUGDISCOVERY
pg no 3

4. pg no 4

5. HISTORYOF HERBSIN DRUGDISCOVERY
Before 20th century the crude and semi pure
extracts of plants, animals, and microbes
represented the only medications available to treat
human and domestic animal illness.
The 20th century revolutionized the thinking in the
use of drugs, as the receptor theory of drug action.
The idea of that effect of drug in human body are
mediated by specific interactions of the drug
molecule with the biological macromolecules
(proteins or nucleic acids in most cases) led
scientists to the conclusion that individual chemical
compounds in extracts are required for the
biological activity of drug.
pg no 5

6. Contd….
This led to beginning of a totally new era in
pharmacology, as pure isolated compounds in
extracts instead of extracts, became the standard
treatment for diseases.
Examples:
1903/04-morphine isolation from opium poppy by
Friedrich Wilhelm.
1899- the first semi synthetic pure drug aspirin, based
on natural product salicin isolated from salix alba was
introduced by Bayer.
1930- sulfonamide antibiotics.
1940-penicillin.
pg no 6

7. pg no 7

8. NATURALPRODUCTDRUGDISCOVERY
PROCESS:
pg no 8

9. Uniquefeaturesofthecompoundsisolatedfromnatural
products
 Greater number of chiral centers
 Increased stearic complexity
 Higher number of oxygen atoms,
 Lower ratio of aromatic ring atoms to total heavy atoms
 Higher number of solvated hydrogen bond donors and
acceptors
 Grater molecular rigidity
 Broader distribution of molecular properties such as
molecular mass and
 diversity of ring systems.
pg no 9

10. Newapproachesin natural product drug discovery
New extract selection and preparation
strategies
Broader bioassays
De-replication
Isolation and structure elucidation
Natural product lead compound for drug
discovery.
pg no 10

11. screening
pg no 11

12. Dereplicationof natural products
pg no 12

13. Identificationof hits
Compound centered approach Traditional
Compound is identified
↓
Biological profile is explored
↓
If compound displays desirable pharmacologic
activity
↓
Compound is refined & developed further
pg no 13

14. pg no 14
The most efficient method
used for screening of herbal
extracts is HTS.
The old laborious processes
involved in the extraction and
isolation were not capable of
generating the numbers which
were required to keep pace
with the HTS
requirements.

15. pg no 15
HIGHTHROUGHPUTSCREENING:
 Simplest target centered approach
 Uses a target based assay & robotic
automation to test thousands of compounds
in a few days time
 2 critical aspects :-
1. A large library of compounds must be
available for screening
2. Assay (Simple/sophisticated) that leads to
rapid identification of true hits must be
developed

16. Leadidentification
Library is “run through” the assay
↓
‘Primary hits’ are examined more closely
↓
Further screening is done (To eliminate false
positives & false negatives)
↓
Leads are advanced in ‘lead optimization’
process
pg no 16

17. pg no 17
Lead optimization
Physical, chemical, biological &
pharmacological properties of
promising lead molecules (that appear
to interact with the target in a desirable
way)
Are Characterized & refined with the
ultimate goal Of selecting a single
molecule to enter into,
Clinical testing & formal drug
development

18. Factors causing termination
 Failure to demonstrate efficacy in a rigorous
animal model of human disease
 Low bioavailability
Extensive/complex metabolism ,Potentially
dangerous reactive metabolites
Toxic effects in preliminary animal toxicology
studies
In vitro evidence that molecule may damage DNA
Extremely difficult chemical synthesis
pg no 18

19. Challengesin natural productbaseddrug discovery
Incompatibility of crude plant extracts with
HTS
Diversion of resources to combinational
chemistry
Technical difficulties
Resupply problem
Policy issues
Financial pressures
pg no 19

20. examples
pg no 20
DRUGS USES
Morphine Analgesic
Artimesinin Anti malarial
Reserpine Tranquilizer
Vincristine/Vinblastine Anti cancer
Taxol Anti cancer
Aspirin(semi synthetic) Analgesic
Digoxin Heart stimulant

21. APPROVALPROCESSOF NEWDRUG
pg no 21

22. Approved drugs based on sources
pg no 22

23. CONCLUSION
Natural products or herbs are the key to drug
discovery.
Herbs are most reliable and efficient source
of drugs.
 Drug discovery from natural products has
reclaimed the attention of the pharma
industry and is on the verge of a comeback
due to new technological inputs that promise
better returns on investment.
pg no 23

24. references
 Discovery and its Relevance to Biodiversity Conservation”, NIH Public Access
Author Manuscript J Nat Prod. Author manuscript; available in PMC 2012 March
25,pg.noPovl Krogsgaard-Larsen,Kristian Stromgaard,Ulf Madsen, ”Textbook of
Drug Design and Discovery”, Fourth edition,2010, published by CPC press,Taylor
and Fransis Group,printed in United states of America,pg.no.-89 to 105.
 R. Mannhold,H.Kubinyi,G.Folkers,”High Throughput Screening in Drug
Discovery”,Volume 35,2006,Edited by J.Huser,WILEY-VCH,pg.no.-20 to 44.
 Spanish National Research Council,”High throughput screening in drug discovery”,
Article in Clinical and Translational Oncology, August 2006,pg.no.-480 to 491.
 Chandra Kant Katiyar, Satyajyoti Kanjilal,”Drug discovery from plant sources: An
integrated approach”, Article March 2012,pg.no.-1 to 11.
 N. Gurnani, D. Mehta, M. Gupta and B.K. Mehta,” Natural Products: Source of
Potential Drugs”, African Journal of Basic & Applied Sciences 6 (6): 171-186, 2014,
IDOSI Publications,pg.no.-1 to 16.
 Service des Sciences de la Vie, Ministère de l’Enseignement Supérieur, de la
Recherche Scientifique et de la Formation des Cadres, Rabat, Morocco, The Success
of Natural Products in Drug Discovery,Received April 25th, 2013; revised May 27th,
2013; accepted June 5th, 2013.
 David G. I. Kingston,” Modern Natural Products Drug .-1 to 18.
pg no 24

25. ThankYou…………………………..
pg no
25