Anthelmintics Agents, Definition, Types, Classification, Structures

1. ANTHELMINTICS
• DEFINITION
•CLASSIFICATION
•DRUGS
Mr. Naga Prashant Koppuravuri, M.Pharm (Ph.D), FAGE.,
Assistant Professor,
Department of Pharmaceutical Chemistry.

2. DEFINITION
Are the agents which are used to
destroy (or) eliminate parasitic
worms (HELMINTH) from the GIT.
act by killing (or) paralysing the
worms.
So that such worms could be easily
expelled out of gut.

3. REPRODUCTION
 These parasitic worms firmly hold the intestinal mucosa and
continue their reproduction by egg production.
 They harm the host by depriving them of
 Food
 Causing blood loss
 Injury to organs
 Intestinal & lymphatic
obstruction
 Secreting toxins

4. ■ Adult filariae live in the lymphatics,
connective tissue or mesentery of host and
produce live embryos or microfilariae,
which goes to blood stream.
■ They are ingested by mosquitoes or similar
insects, they develop to larvae in
secondary host and pass to mouth parts of
insect and
re-injected to humans

5. TYPES OFWORMS
■ Cestodes (tape worm)
■ Nematodes (round worm)
■ Trematodes (Flukes)

6. Ascaris lumbricoids ( common round worm)

7. filariasis

8. Hookworm

9. Pinworm male ,female

10. Tapeworm

11. whipworm

12. TYPES OF ANTHELMINTICS
■ Depending upon the action, anthelmintics can be categorised
into
■Vermifuges expel the worms
from the body
■Vermicides kill the worms in
the body

13. Chemical Classification
1. Benzimidazoles- mebendazole, albendazole thiabendazole.
2. Quinolines & isoquinolines- oxaminiquine praziquantel.
3. Pierazine derivatives- piperazine, diethylcarbamazine.
4. Vinyl pyrimidines- Pyrantel pamoate, oxantel
5. Amides- Niclosamide
6. Natural products- Ivermectin
7. Organo phosphorous compounds- Metrifonate
8. Imidazolothiazoles-Levimazole
9. Nitro derivatives-Niridazole

16. MEBENDAZOLE
■ Vermox
■ Methyl-5-benzoyl-2-benzimidazolyl carbamate.
■ MOA- It irreversibly blocks glucose uptake in susceptible
helminths, therby depleting glycogen stored in the parasite.
■ It does not affect glucose metabolism in the host.
N
H
N
NH COCH3
O
C

17. USES
■ Effective against
■ Whip worm (Trichuria )
■ Pin worm(Enterobius vermicularis)
■ Hook worm
■ Ascaris lumbricoides

18. SYNTHESIS
C
SCH3
H2N NH
ClCOOCH3
S-methyl thio urea
methyl chloro
formate
C
SCH3
H2N NCOOCH3
NaOH
PH 8
Methyl-s-methyl
thio urea carbamate
STEP 1
STEP 2
O
C
Cl
4-Chloro benzo
phenone
HNO3
O
C
Cl
NO2
NH3
O
C
NH2
H2-Pd-C
NO2
O
C
NH2
NH2
C
SCH3
H2N NCOOCH3
O
C
N
H
N
NHCOOCH3
-NH3
-CH3SH

19. ALBENDAZOLE
■Eskazole, Zentel
■Methyl 5-(propylthio)-2-benzimidazole carbamate
■Widely employed throughout the world for the treatment of intestinal
nematode function.
■Is effective as a single dose treatment for
Ascariasis
Hookworm infections
Trichuriasis
N
H
N
NH COOCH3
S

20. THIABENDAZOLE
 Mintezol
 2[4-thiazolyl]benzimidazole
N
H
N
S
N

21. MECHANISMOF ACTION
 bind with β-tubulin and inhibit microtubule polymerization.
 β-tubulin is the precursor of formation of microtubules.Thereby
arrest in cell division in nematodes.
■Biochemical Changes
■Inhibition of mitochondrial fumerate reductase
■Reduced glucose transport
■Uncoupling of oxidative phosphorylation

22. THIABENDAZOLE (cont)
■It has a broad spectrum anthelmintic activity.
■Used to treat
■Enterobiasis (thread worm)
■Ascariasis (round worm)
■Trichuriasis (whip worm)
■In addition to its use in human medicine, it is
widely employed in vertinary practice to control
helminths.

23. SYNTHESIS
NH2
S
N
C
N
Aniline cyano thiazole
NaOCl
N
H
C
N
Cl
S
N
N
H
N
S
N
NH4OH

24. OXAMNIQUINE
■ Vansil
■ 1,2,3,4-tetrahydro-2-[isopropyl-amino) methyl]-7-nitro-6-
quinoline methanol.
■ It inhibits DNA, RNA & protein synthesis.
■ SAR- OH group is essential for activity.
■ For the treatment of intestinal schistosomiasis.
N
H
O2N
HOH2C
CH2NHCH

25. PRAZIQUANTEL
■ Biltricide
■ 2-(cyclohexyl carbonyl)-1,2,3,6,7,11b-hexahydro-4H-
pyrazino[2,1-a]isoquinolin-4-one.
■ It increases cell membrane permeability of susceptible worms,
resulting in loss of intracellular calcium and loss of extracellular
sodium.
N
N
C
O

26. ■ Massive contractions & ultimate
paralysis of the fluke musculature occurs.
■ The worms lose grip of intestinal mucosa
and are expelled.
■ USE- It has become the agent of choice
for the treatment of infections caused by
fluke infections

27. PIPERAZINE CITRATE
 Artheriticine, Dispermin
 MOA: It blocks the response of the ascaris muscle to acetyl
choline, causing the flaccid paralysis in the worm, which is
dislodged from the intestinal wall and expelled in the feces.
 Highly effective againstAscaris lumbricoides & Enterobius
vermicularis.(Round worm & thread worm)
N
H
H
N

28. SYNTHESIS
HO
NH2
H2N
OH
-2H20
HEAT
HN
NH

29. DIETHYL CARBAZINE
CITRATE
 HETRAZAN
 N,N-diethyl-4-methyl-1-piperazine carboxamide
N
N
H3C
CO N
C2H5
C2H5

30. Mechanism Of Action
■Immobilizes microfilariae and alters their surface structure,displacing them from
tissues & making them susceptible to destruction by host defense mechanism
■ It has immunosuppressive effects
■Filariasis and ascariasis

32. Pyrantel Pamoate Pin-X

34. Oxentel
Oxantel pamoate is an agonist of the acetylcholine receptors in the
muscle of nematodes and causes paralysis.

35. NICLOSAMIDE
■ Cestocide, Mansonil,Yomesan
■ 5-chloro-N-(2-chloro
-4 nitrophenyl)-2-hydroxy
benzamide
■ MOA:The drug inhibits anerobic phosphorylation ofADP
by the mitochondria of the parasite, and interfering with
anerobic generation of ATP by theTape worm.
■ So it inhibits seperation and blocking glucose absorption
by the intestinal nematode function.
OH
Cl
C
O
NH NO2
Cl

36. ■ SAR- For the activity, the OH group of benzoic acid moiety had
to be in 2 nd position.
■ Uses-Agent for choice for the treatment ofTaenia solium and
Taenia saginata.
■ A saline purge 1-2 hr after the ingestion of this drug is
recommended to remove the damaged scolex & worm
infections.
■ Quinacrine can aid for this purpose.

37. IVERMECTIN
O
CH3
O
HO
H
H
OH
O
O
CH3
CH3
H3C
CH3
H3C
H
H
O
H
CH3
O
CH3
O
O
OH
OH3C
CH3
H

38. ■ Are a mixture of 22,23dihydro derivatives of avermectins B1a
&B1b prepared by catalytic reduction.
■ Are members of a family of structurually complex antibiotics
produced by a strain of Sterptomyces avermilitis.
■ The structures of avermectins were established by a
combination of spectroscopic and X-ray crystallographic
techniques to contain pentacyclic aglycone glycosidically linked
at 13 th position to a disaccharide that comprises two
oleandrose sugar residues.
■ MOA- It blocks interneuron transmission in nematodes by
stimulating the release of inhibitory neurotransmitter γ-amino
butyric acid-GABA.
■ Uses- widespread use in veterinary practice in the treatment of
Onchocerciasis caused by Oncocerca volvulus.

39. Levimazole
Metrifonate
Niridazole