This presentation discusses in detail about , the way natural products have paved the way forward for the discovery and introduction for new drugs/medicines. The leads from nature are narcotics, antihypertensives, anticancer agents and so

1. Dr.Vinod B
Dept of Pharmaceutical Chemistry
St.Joseph’s College of Pharmacy,Cherthala
1

3.  Large No. of Pharmaceuticals derived from
natural sources.
 Few examples are :
 Artemisnin
 Alkaloids(Quinine, Morphine, Codeine, )
 Antibiotics (Penicillin,Cephalosporin etc)
 Anticancer agents (Paclitaxel )
3

4.  Morphine isolated in
the year 1803 by
Serturner ,German
Pharmacist
 Phenanthrene nucleus
O
H
O
H
1
11
2
12
3
4
10
9
13
14
5
6
8
7
15 16
N
17
H
O
CH3

5.  Source –Dried latex
of Opium poppy
 Numerous
alkaloids-
Morphine,Codeine,
Narcotine,
Papaverine etc

6.  Drugs derived from Morphine
 Codeine ( Methyl Morphine)
 Heroin (Diacetyl Morphine)
6

7. 7

8.  Naturally occuring Morphine derivative –
Codeine (methyl morphine)analgesic and
antitussive action,
CH3
C
H3
O
H
O
1
11
2
12
3
4
10
9
13
14
5
6
8
7
15 16
N
17
H
O

9.  Earliest semisynthetic derivative –
Heroin(Diacetyl morphine)-used in terminal
cancer-
CH3
CH3
O
O
C
H3
O
O
1
11
2
12
3
4
10
9
13
14
5
6
8
7
15
16
N
17
H
O

10.  Modification of C-ring of morphine -N-
Demethylation and re-alkylation yields N-
allyl morphine –nalorphine-morphine
antagonist
O
H
O
H
O
C
H2
1
11
2
12
3
4
10
9
13
14
5
6
8
7
15 16
N
17
H

11. Further modification–Naloxone –little agonistic
activity –retained in therapy for treatment of
opiate induced respiratory depression.
CH3
O
O
H
O
1
11
2
12
3
4
10
9
13
14
5
6
8
7
15 16
N
17
H

12. Further modification–Naloxone –little agonistic
activity –retained in therapy for treatment of
opiate induced respiratory depression.
CH3
O
O
H
O
1
11
2
12
3
4
10
9
13
14
5
6
8
7
15 16
N
17
H

13.  Modification of C ring fromThebaine using
Diel’s-Alder reaction-Etorphine and
Buprenorphine.
CH3
CH3
CH3
C
H3
O
C
H3
O
O
N
O
H
CH3
CH3
CH3
CH3
C
H3
O
C
H3
O
O
N
O
H
CH3

14.  Morphine lacking dihydro furan ring-
morphinans-analgesic and additive
properties
1
11
2
12
3
4
10
9
13
14
5
6 8
7
15 16
NH
17
H

15.  Taxols derived fromYew tree
 YewTree
 Regarded as the tree of death.
15

16.  Taxus Buccata used for funeral wreaths
 Used to prepare arrow poison by Celts.
16

17.  T.Brevifolia yielded Paclitaxel.
17
Docetaxel derived from Paclitaxel
by modifying the ester side chain.

18. 18

19.  Mevastatin isolated from Penicillium Citrinium
by Dr Akira Endo(1970)
19

20.  Lovastatin isolated from Aspergilus terreus
20

21. 21

22.  S A R of Statins
 Lactone ring, bicyclic structure & ethylene
bridge
 Size & shape of ring
 Nature of ester moiety
22

23.  Simvastatin
side chain branching Pravastatin
lactone ring opening
23

24.  Atorvastatin , Rosuvastatin-Ar ring replaced
by other rings
24

25.  Anticoagulant prevents or reduce coagulation
of blood, thus prolong clotting time of blood.
25

26.  Dicoumarol is the natural lead
26

27.  Dicoumarol- slow & erratic onset of action
 Warfarin –potent drug with increased
duration of action
 Acenocoumarol –Rapid onset of action
27

28.  Teprotide -Antihypertensive
 Ferreira et al isolated a family of peptides
from pit viper (PothrosJararaca) venom-
inhibited decomposition of Bradykinin by
inhibiting ACE
28

29.  Teprotide structure (nona peptide.)
29

30. Etoposide &Teniposide
 Lignan Podophyllotoxin analogues
 Ancient folk remedy for gout
 May apple(Podophyllum peltatum)
30

31.  Podophyllotoxin
31

32.  Iso podo phyllotoxins
 Teniposide Etoposide
32

33.  Isopodophyllotoxins causes DNA single
stranded and double stranded breaks & DNA
protein links.
 Inhibition ofTopoisomerase II
 Action most prominent in late S or early G-2
phase
33

34.  MOA
34

35.  Etoposide
 Refractory testicular tumours,small cell lung
cancer
 Teniposide
 Acute non lymphocytic leukemia, Hodgkin’s
disease, Kaposi’s sarcoma,neuroblastoma
35

36.  Cinchona bark used by South Americans to cure
fevers
36

37.  Introduced to Europe by Jesuit priests, in 17th
century.
 Quinine not very potent or long acting.
37

38.  Discovered the antimalarial potency of 4,6
and 8-amino quinolines.
 Pamaquine,Primaquine, Chloroquine etc
38

39.  Artimisnin from Artemesia Annua, a Chinese
herb.
39

40. 40
Artemisnin
Arteether

41.  Macrolide-Large macrocyclic
lactone,desosamine & cladinose sugars(C5 &
C3)
 Streptomyces species
 Eg. Erythromycin (natural) -14-member cyclic
lactone
41

42.  Azithromycin (semi synthetic)-15 membered
cyclic lactone
42

43.  Roxithromycin
43

44.  Clarithromycin
44

45.  MOA
 Inhibits protein biosynthesis through
interaction with 50 S sub unit of bacterial
ribosome.
45

46.  History begins with Sir Alexander Fleming
46

47. 47

48. 48

49.  MOA
 Inhibit D-alanyl-D-alanine transpeptidase
activity by forming stable esters with opened
lactam ring .
 Ability to inhibit enzymes depends upon
conformational similiarity between amide
bond of β lactam ring and peptide link of D-
alanyl-D-alanine.
49

50.  CEPHALOSPORINS
 Antibacterial activity of metabolite of
Cephalosporium acremonium detected by
Brotzu- isolation of Cephalosporin C by
Abraham (1945)
50

51.  General structure
51

52.  Cephalosporins Classification
52

53.  Penems not found in nature
53

54. Clinically relevant
Imipenem-cilastatin,meropenem and
ertopenem
54

55.  Skeletal muscle relaxants during surgery
developed from studies about South
American arrow poisons as well as blow pipe
poisons
55

56.  King isolated D-tubocurarine from tube
curare plant
56

57.  D-tubocurarine led to many synthetic
bisquarternaries(eg;decamethonium)
 Suxamethonium
57

58.  D-tubocurarine(long duration of action) led to
drugs like laudexium & atracurium
58

59. 59