This document discusses structure-activity relationships (SAR) through examples of different drug molecules. It provides details on the chemical structures of camptothecin (CPT), taxol, and the flavonoid quercetin and how specific structural features relate to their biological activities. For CPT, rings A-D and the stereochemistry at C-20 are essential for anti-tumor activity, while modifications to rings C and D eliminate activity. The ester linkage and phenylisoserine chain of taxol are required for its anticancer effects. For flavonoids like quercetin, features important for radical scavenging include a catechol structure in ring B and hydroxyl groups that enable hydrogen bonding and electron de

1. STRUCTURE ACTIVITY
RELATIONSHIP
Abdul Samad
Dr. Syed Badshah
1

2.  Structure
 Activity
 SAR (Discussion/Elaboration)
Contents
2

3. 3
Crude drug Structure Ligand bindingReceptor
Biological
response

4. 4
CHEMICAL STRUCTURE
 A chemical structure includes molecular geometry,
electronic structure, and crystal structure of a molecule.
BIOLOGICALACTIVITY
 Biological activity is an expression describing the beneficial
or adverse effects of a drug on living matter.

5. 5
STRUCTURE ACTIVITY RELATIONSHIP
 The relationship between the chemical or 3D
structure of a molecule and its biological activity.
Enables the determination of the chemical groups
responsible for evoking a target biological effect in
the organism.

6. 6
WHY SAR Exist?
• The interaction of the drug molecule with protein depends
on its chemical structure
NEED OF SAR STUDY
• A study of the structure–activity relationship is mainly
done by lead molecule.
• It is used to determine pharmacophore, unwanted side
effects
• To develop a new drug that has increased activity.

7. 7
Cont.…..
• To determine some different activity from an
existing drug
• To fewer unwanted side effects
• To know the changes in pharmacological properties
by performing minor changes in the drug molecule

8. 8
SAR (DISCUSSION/ELABORATION)
FFFFFFFFFFFFFFFFFollowing
cALKALOIDSCFLAVONOIDS TERPENOIDS

9. 9
TAXOL CPT

10. 10
Camptothecin
(CPT)
WALL & WANI in
early Sixties
Camptotheca
cuminata,Tree of
Joy, Love
Quinolino
alkaloid
Pentacyclic
ring
structure

11. 11
STRUCTURE OF CPT WITH IUPAC
NAME

12. 12
A B C
D
E
Rings A–D are essential for activity. Saturation of ring B< activity
necessary for activity
essential for activity, S N
inactive
D-ring pyridone is required for anti
tumor activity.
 Modifications in rings A, B are well tolerated
The stereochemistry at C-20 is very crucial as
20(S) hydroxyl is active, 20(R) inactive
modifications at the C , D rings led
to complete loss of cytotoxicity.

13. 13
Modification in rings A,B
Topotecan
Irinotecan

14. 14
Modification in rings C,D
 In general, modifications at the C and D rings of
camptothecin led to complete loss of cytotoxicity.
 If we see these rings, the only positions available
for modifications are C-5, C-14 and C-17. Several
derivatives have been reported either with less
activity or with loss of activity.

15. 15
Modification in ring E
 The α- hydroxyl lactone system of ring E has been
found to be important for the inhibition of the
topoisomerase enzyme as well as for in vivo
potency
 Derivatives having a lactam group instead of a
lactone, were devoid of topoisomerase inhibitor
activity.

16. 16

17. 17
TAXOL
Taxol, paclitaxel, trade name taxol,
by Dr. WALL and Dr. WANI
Complex
polyoxygenated
diterpenoid
Pacific yew, Taxus
brevifolia
basic [9.3.1.0]
Pentadecane, tetracyclic
ring system.
N-benzoyl-b-phenyl
isoserine side chain, at
the C-13 hydroxyl as an
ester linkage.

18. 18
STRUCTURE OF TAXOL WITH IUPAC NAME

19. 19
Oxitane ring essential
Ester, Amino
ester,epimer,deoxy =
active
Reduction enhance activity
Removal of acetyl < activity
Phenyl isoserine chain essential for activity
N-acyl group, required
Aryl group, essential
Free OH active in both(in vivo, in vitro)
Ester only in vivo
The C-3’aryl group is required for better
activity, methyl group, activity is reduced19-
fold.
northern and southern hemispheres.
modifications in the southern hemisphere are strictly forbidden
while in the northern hemisphere are allowed

20. 20
C-13 SIDE CHAIN
 C-13 side chain is essentially required for anticancer
activity. The C-2’-hydroxyl is important for activity.
 When this hydroxyl is protected, activity is reduced to a
great extent and if the protection is made with a labile
group it shows similar activity in vivo, while no activity is
shown in in vitro testing

21. 21
FLAVONOIDS
QUERCETIN

22. 22

23. 23
The main structural features of flavonoids required for
efficient radical scavenging could be summarized as
i. An ortho-dihydroxy (catechol) structure in the B
ring, for electron delocalization

24. 24
 2,3-double bond in conjugation with a 4-oxo function in
the C ring provides electron delocalization from the B ring

25. 25
 Hydroxyl groups at positions 3 and 5 provide hydrogen
bonding to the Oxo group

26. 26
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