The document discusses the history and treatment of amoebiasis, an infection caused by the parasite Entamoeba histolytica. It outlines the discovery of the parasite, evolution of medication including various anti-amoebic drugs, and their mechanisms of action. The document emphasizes that amoebiasis is curable and describes the effectiveness and side effects of specific treatments.

1. ANTI-AMOEBICS
NISHU SINGLA
ASSISTANT PROFESSOR
DEPT. OF PHARMACEUTICAL CHEMISTRY
ISF COLLEGE OF PHARMACY
WEBSITE: - WWW.ISFCP.ORG
EMAIL: NISHU131989@GMAIL.COM
ISF College of Pharmacy, Moga
Ghal Kalan,nGT Road, Moga- 142001, Punjab, INDIA
Internal Quality Assurance Cell - (IQAC)

2. HISTORY OF DISCOVERY 2
• Parasitic infections in humans are not a recent phenomenon. Bloody, mucous diarrhea was
the earliest record of the symptoms of the disease; from the Sanskrit document Brigu-
samhita, which was written at around 1000BC.
• Around the 16th century, amoebiasis became more widespread in the developed world.
• Protozoans were difficult to identify before the invention of the microscope in the 17th
century due to their small size.
• The causal agent, Entamoeba histolytica, was discovered in Russia in 1873 by Friedrich
Losch. His early observations came from the case of a young farmer who had been
suffering from chronic dysentery. Losch found large numbers of amoeba in his feces and
associated the amoebas to be the cause of the dysentery.

3. 3
• In 1925, Emile Brumpt suggested that there must be two species: one that is invasive while
the other is not (which he named E. dispar) because for a long time, it was known that
people who were infected with E. histolytica never developed symptoms and spontaneously
clear the infection.
• In 1969, WHO defined amoebiasis as “infection with Entamoeba histolytica, with or
without clinical manifestations”, thus implying that all the strains were potentially
pathogenic.
• In 1993, due to biochemical, immunological and genetic data that supports this view, a
formal redescription of E. histolytica was published--with the invasive species named E.
histolytica and the non-invasive species named E. dispar.
• 1997 WHO meeting in Mexico City led to clear guidelines distinguishing the two species.

4. 4EVOLUTION OF MEDICATION
 The history of medication for amoebiasis dates back to 1912 when Leomard Rogers
developed the injectable emetine. Later in 1948, chloroquinine was employed for the
treatment of amoebiasis. In year 1952, dehydroemetine was used. From the year 1966
onwards, Nitro-imidazole derivatives such as Metronidazole, Tinidazole were employed as
the first class drugs for the treatment of amoebiasis.

5. 5INTRODUCTION
 Amoebiasis is an infection with Entamoeba histolytica produced by the ingestion of cysts
of this organism. Amoebiasis can be asymptomatic or can lead to severe, life-threatening
dysentery. The organism exists in two forms, the motile trophozoite form or the dormant
cyst form.
 In the intestine, the cysts develop into trophozoites that adhere to colonic epithelial cells
by means of lectin on the parasitic membrane, which has similarity to the host adherence
proteins.
 The trophozoite then lyses the host cell (hence histolytica) and invades the submucosa,
where it may secrete a factor that inhibits IFNY- activated macrophages, which would
otherwise kill it. These processes may result in dysentery

6. 6
 The parasite may invade the liver, leading to the development of Liver abscesses. The
cysts can survive outside the body for at least a week in a moist and cool environment.
The cyst form is responsible for the transmission of the disease. The cyst is spread by the
direct person-to-person contact.
PASSAGE OF
AMOEBIC
INFECTIONS
IN HUMANS

7. 7ANTI-AMOEBICS
 Definition: Anti-amoebic agents are the drugs used in the treatment of amoebiasis, the
potential drug should be active within the bowel lumen in the bowel wall and
systematically particularly in the liver.
 Amoebiasis is a readily curable condition which responds promptly and completely to
correct management. There is no evidence of natural or acquired resistance by
Entamoeba histolytica to amoebicides.
 Many drugs are effective but none is ideal.
 The principles of drug therapy in amoebiasis are simple. The aim is to eradicate
E.histolytica which may be present in any or all of the following sites: in the bowel
lumen; in the bowel wall; systemically, chiefly in the liver.

8. 8
 For the acute invasive intestinal amoebiasis resulting in acute severe amoebic dysentery
e.g. metronidazole or Tinidazole followed by Diloxanide.
 For the hepatic amoebiasis, metronidazole is employed followed by Diloxanide.
 For chronic intestinal amoebiasis and carrier state, Diloxanide is used.

9. 9CLASSIFICATION
1. ON THE BASIS OF THEIR SITE OF ACTION:
A. Luminal (intestinal) amoebicides- Diloxanide furoate
Iodoquinol
Chloroquinol
B. Intestinal trophozoitocidal agents- Paramomycin
Erythromycin
Metronidazole
Tinidazole
Tetracycline

10. 10
C. Systemic amoebicides-
(i) Not acting locally in the intestine - Emetine
Dehydroemetine
Chloroquinine
(ii) Acting both in intestine and extra-intestine- Metronidazole
Tinidazole
II. SYNTHETIC AND NATURAL SYNTHETIC DRUGS-
A. Dichloro-acetamide derivatives- Diloxanide furoate
B. 8-Hydroxy quinolones- Iodoquinol
Chloroquinol

11. 11
C. Nitro-imidazole- Metronidazole
Tinidazole
D. Natural derivatives- Emetine
Dehydroemetine
Paramomycin

12. 12
S.No. Name of the drug Structure IUPAC
Side effects or
Adverse effects Specific use Assay Method
A. Dichloro-acetamide Derivatives
1 Diloxanide furoate 2-[p(N-methyl-2,2-
dichloro)acetamide]
phenyl furoate
Flatulence, itchiness,
and hives.
Treatment of intestinal
amoebiasis & hepatic
amoebiasis
Spectrophotometric
method.
B. 8-Hydroxy quinolones Derivatives
2 Iodoquinol OR
Diiodohydroxy
quinoline
5,7-diiodo-8-hydroxy
quinoline
Loss of visual activity
and even blindness at
higher doses
Intestinal amoebiasis. Chromatogrphic
methods
3 Chloroquinol OR
Quiniodochlor OR
clinoquinol
5-chloro-7-iodo-8-
hydroxy quinoline
Nausea,
Skin rash,
Stomach upset,
Acute toxicity,
Transient loose
Green stools
Antifungal, used in the
inflammatory skin
disorders.
ELISA method
TABLE OF ANTIAMOEBIC DRUGS

13. 13
S.No. Name of the drug Structure IUPAC
Side effects or
Adverse effects Specific use Assay Method
C. Nitro-Imidazoles Derivatives
4 Metronidazole 2-Methyl-5-nitro-1-(2-
hydroxyethyl) imidazole
nausea, diarrhea, weight
loss, abdominal pain,
vomiting, headache,
dizziness, and metallic
taste in the mouth
Giardiasis,
Trichomoniasis,
Bacterial vaginosis
Spectrophotometric
assay
5 Tinidazole 2-Methyl-5-nitro-1-(2-
ethyl sulfonyl ethyl)
imidazole
upset stomach, bitter
taste and itchiness,
Headache, physical
fatigue, and dizziness.
for infections from
amoebae, giardia, and
trichomonas
Spectrophotometric
analysis

14. 14
S.No. Name of the drug Structure IUPAC
Side effects or
Adverse effects Specific use Assay Method
D. Natural Synthetic Drugs
6 Emetine 2-[(6,7-Dimethoxy-
1,2,3,4-
tetrahydroisoquinolin-1-
yl)methyl]-3-ethyl-9,10-
dimethoxy-,3,4,6,7,11-
hexahydro-1H-
pyrido[2,1]isoquinoline
Nausea, risk of
developing proximal
myopathy and/or
cardiomyopathy.
Effective against the
tissue trophozoites, used
in the laboratory to
block protein synthesis
in eukaryotic cells.
High-performance liquid
chromatographic
technique
7 Dehydroemetine 2-[(6,7-Dimethoxy-
1,2,3,4-
tetrahydroisoquinolin-1-
yl)methyl]-3-ethyl-9,10-
dimethoxy-4,6,7,11b-
tetrahydro-1H-
pyrido[2,1-
a]isoquinoline
Cardiac dysrhythmia,
Diarrhea, Hypotension,
Muscle pain, Nausea etc.
an investigational drug
for the treatment of
metronidazole-resistant
amoebiasis,
in treatment of herpes
zoster
Spectrofluorometric
determination
N
HN
OCH3
OCH3
CH3
H3CO
H3CO
H
N
HN
OCH3
OCH3
CH3
H3CO
H3CO
H
H

15. 15
SYNTHESIS OF ANTIAMOEBIC DRUGS:
1. Dichloroacetamide derivatives: Diloxanide Furoate
NH2OH OH NH CO
Cl
Cl
OCOCH3 NH CO
Cl
Cl
OCOCH3 N
CH3
CO
Cl
Cl
p-amino phenol
OH N
CH3
CO
Cl
Cl
O
O
O
NH
O
Cl
Cl

16. 16MECHANISM OF ACTION:
 Diloxanide furoate, a Dichloroacetamide derivative is a very effective luminal amoebicide
for the cyst passers.
 It directly kills the trophozoites. It has no anti-bacterial activity.
USES:
 Diloxanide furoate is used along with tetracycline and chloroquinine in the treatment of
intestinal amoebiasis and hepatic amoebiasis.

17. 172. METRONIDAZOLE SYNTHESIS
H2N
H2
C
H2
C NH2
CH3CN
N
H
N
CH3
N
H
N
CH3O2N
ClCH2CH2OH
N
N
CH3O2N
CH2CH2OH
HNO3P2O5
Reflux
Metronidazole

18. 18MECHANISM OF ACTION:
The action of metronidazole is thought to be the damage to the DNA of the trophozoite by toxic
oxygen products generated from the drug by the parasite.
Metronidazole kills the trophozoites of E.histolytica but has no effect on the cysts. It is the most
effective drug available for the invasive amoebiasis involving the intestine or the liver, but it is
less effective against the organism in the liver or the gut.
USES:
Metronidazole is primarily used to treat: bacterial vaginosis, pelvic inflammatory disease (along
with other antibacterial like ceftriaxone), pseudomembranous colitis, aspiration pneumonia,
rosacea (topical), fungating wounds (topical), intra-abdominal infections, lung abscess,
periodontitis, amoebiasis, oral infections, giardiasis, trichomoniasis, and infections caused by
susceptible anaerobic organisms such as Bacteroides, Fusobacterium, Clostridium,
Peptostreptococcus, and Prevotella species.
It is also often used to eradicate Helicobacter pylori along with other drugs and to prevent
infection in people recovering from surgery.

19. 193. TINIDAZOLE:
H2N
H2
C
H2
C NH2
CH3CN
N
H
N
CH3
N
H
N
CH3O2N
ClCH2CH2OH
N
N
CH3O2N
H2C
HNO3P2O5
Reflux
CH2
S O
O
H2
CH3C
Tinidazole

20. 20
 In anaerobic micro-organisms, Tinidazole is converted to active form by reduction of its
nitro group, this gets bound to DNA and prevents nucleic acid formation. It is a broad
spectrum of protozoal and anti-microbial activity.
USES:
 A large body of clinical data exists to support use of Tinidazole for infections from
amoebae, giardia, and trichomonas, just like metronidazole. Tinidazole may be a
therapeutic alternative in the setting of metronidazole tolerance. Tinidazole may also be
used to treat a variety of other bacterial infections (e.g., as part of combination therapy for
Helicobacter pylori eradication protocols).
MECHANISM OF ACTION: