LEAD IDENTIFICATION for pharmacognosy

1. LEAD IDENTIFICATION
Presented by:-
Tejaswini C
M.Pharm

2. STEPS IN DRUG DESIGNING
TARGET IDENTIFICATION
TARGET VALIDATION
LEAD IDENTIFICATION
LEAD OPTIMIZATION
DOCKING
PRECLINCAL & CLINCAL TRIALS

3. LEAD IDENTIFICATION
• A LEAD is a compound (usually a small organic molecule) that
demonstrates a desired biological activity on a validated molecular
target.
• The compound must exceed a specific potency threshold against
the target.
• The compound used as potential leads can be from many
sources . The most important sources of leads is libraries of
molecules.

4. lead identification process
Structure based drug design
• Docking
• Denovo
• Virtual screening
• Combinatoral library
building
• Binding energy predictions
ligand based drug design
• Pharmcophore based
screening
• QSAR
• Shape based screening
• ADME
• Toxicity

5. Methods of lead discovery
• They are several apporaches which can be employed for
lead identification.
• In order to identify a lead nucleus in a given series, the
whole series should be analysed for a particular
biological activity.
• Once the lead is identified, it can be structurally
modified to improve the potency.

6. Important methods for lead identification.
• Isolation of bioactive compound from natural sources
• Accidental screening
• Random screening
• Non –random screening
• Drug metabolism studies
• Clinical observations
• Interferences with fundamental life process
• Exploitation of side effects of drugs
• Rational approaches to lead discovery

7. Isolation of bioactive compound from
natural source
• plants are consider as one of the richest source of
lead compounds.
• most of biological active natural products are plant
secondary metabolites with complex structures.
• Eg:- Morphine – Papaver somniferum
Digoxin- Digitalis
Quinine- Cinchona
Accidental screening
Eg:- pencillin, mustine,nitrous oxide, cisplatin etc.

8. Random screening
• In this method, all compounds (including synthetic
chemicals and natural products of plant, marine &
microbial origin) from a given series are tested.
• Inspite of budgetary & manpower overuse, this
method may be used to discover drugs or leads that
have unexpected activities.
• Antibiotics like streptomycin & tetracycline were
found out by this method.

9. Non- random screening
• It is a modified form of random screening.
• which was developed because of budgetary &
manpower restrictions.
• In this method, only such compounds having similar
structural skeletons with that of lead, are tested.

10. Drug Metabolism studies
• Metabolism of drug occurs as an attempt by
metabolizing enzymes to cut short the period of stay
of the drug in the body.
• Structural modifications are done in drug molecule by
the enzymes to increase the polarity.
• It is brought about regardless of whether the
resulting drug metabolite possesses more activity or
toxicity.
• The discovery of paracetomol is reported through
the metabolic studies of acetanilide.

11. Clinical observations
• Many times the drug possesses more than one
pharmacological activities.
• The main activity is called as therapeutic effect
while rest of the actions are known as side effects
of the drug.
• such drug may be used as lead compound for
structural modifications to improve the potency of
secondary effects.
• eg:- sulphonamide oral hypoglycemics

12. Interference with fundamental life
process
• Lead can be obtained by interfering with life
process such as krebs cycle, protein biosynthesis
etc.
• Eg:- Sulphonilamide block the synthesis of folic acid
by competing with improperation of PABA
Exploitation of side effects of drugs
• Anti hypertension drug minoxidil posses unwanted hair
growth as a side effect, based on this development of hair
growth promoters is done.

13. Rational approaches to lead discovery
• This approach is greater importance in identification of
lead nucleus. it involves the use of sign & symptoms of
the disease.
• most diseases, atleast in part,arise from an imbalance of
particular endogenous bioactive substances in the body.
• these imbalances may be corrected by agonism or
antagonism of a receptor or by inhibition of particular
enzyme.
• once the real site of such imbalance is identified , the
natural enzyme substrate or endogenous substance may
be used as lead nucleus.
• Eg:- endogenous hormones, progestrone & 17β-estradiol
were used for developing oral contaceptives.

14. Refrences
• Kulkarni V.M, Bothara k.G. DRUG DESIGN. Nirali
prakashan.
• Vogale’s drug discovery and evaluation.

15. Thank you