SAR and Mechanism of action for Antiprotozoal agents.

1. ANTIPROTOZOAL DRUG
DR. MANJOOR AHAMAD SYED,
M.Pharm,Ph.D
Associate. Professor
Department of Medicinal Chemistry,
College of Public Health and Medical Sciences,
Mettu University, Mettu
Post Box No-318
Ethiopia.

2. ANTIPROTOZOAL DRUG
DEFINATION:
Antiprotozoal drugs are used to treat a variety of diseases caused by protozoa.
Anti protozoal drug use for fallowing
protozoal diseases are
 Amebiasis
 Malaria
 Trypanosomiasis
 Leishmaniasis
 Giardiasis

3. Amebiasis (also called amoebic dysentery) is an infection of intestinal tract caused
by Entamoeba histolytica.
The disease can be acute or chronic, with the patients showing varying degrees of
illness, from no symptoms to mild diarrhea to fulminating dysentery (Dysentery in
which the symptoms are intensely acute, leading to prostration, collapse and often
death).

5. LIFE CYCLE OF ENTAMOEBA HISTOLYTICA
Life cycle
Life cycle consists of following steps:
1. Ingestion of cyst
Cysts are ingested through feces, contaminated food or water.
2. Formation of trophozoites
Cysts are passed in to the lumen of intestine, where the trophozoites liberated.
Entamoeba histolytica exists in two forms:
a. Cyst form (Which can survive outside of the body).
b. Trophozoites form (Which are labile and don’t persist outside of the body).

6. 3. Penetration and multiplication of trophozoites
Trophozoites are penetrated in intestinal wall and multiply within colon wall.
They either invade and ulcerate the mucosa of large intestine or simply feed on
intestinal bacteria.
4. Systemic invasion
Large numbers of trophozoites within the colon wall can also lead to systemic
invasion and caused liver abscess.
5. Cysts discarded
The trophozoites within the intestine are slowly carried towards the rectum,
where they return to cyst form and are excreted in feces.

7. ANTIAMOEBIC DRUGS
These are the drugs useful in infection caused by protozoa Entamoeba histolytica.
1. Tissue amoebicides
a. For both intestinal and extraintestinal amoebiasis
i. Nitroimidazoles: Metronidazole, Tinidazole, Secnidazole, Ornidazole,
Satranidazole
ii. Alkaloids: Emetine, Dehydroemetine
b. For extra intestinal amoebiasis only: Chloroquine
2. Luminal amoebicides
a. Amides: Diloxanide furoate, Nitazoxanide
b. 8-Hydroxyquinolines: Quiniodochlor (Iodochlorohydroxyquin, Clioquinol),
Diiodohydroxyquin (Iodoquinol)
c. Antibiotics: Tetracyclines

8. METRONIDAZOLE USES:
1. Metronidazole is an antibiotic. It's
used to treat skin infections, rosacea
and mouth infections (including
infected gums and dental abscesses).
2. It's used in the treatment of conditions
such as bacterial vaginosis and pelvic
inflammatory disease.
3. It is also used to treat parasitic
infections including Giardia infections
of the small intestine, amebic liver
abscess, and amebic dysentery
(infection of the colon causing
bloody diarrhea), bacterial vaginosis,
trichomonas vaginal infections, and
carriers of trichomonas (both sexual
partners) who do not have symptoms
Adverse effects:
Dizziness, headache,
stomach
upset, nausea, vomit
ing, loss of appetite
or metallic taste in
your mouth may
occur.
N
N
CH2CH2OH
CH3
O2N
2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol
Synthesis:
NH2
N
H2
ethane-1,2-diamine
CH3CN/S/Zn N
N
H
CH3
HNO 3/P2O5
N
N
H
CH3
O2N
ClCH 2CH2OH/ 
N
N
CH2CH2OH
CH3
O2N
Metronidazole
2-methyl-1H-imidazole 2-methyl-5-nitro-1H-imidazole
- HCl

9. METRONIDAZOLE
 Mixed amoebicide.
 Drug of choice for intestinal & extraintestinal
amoebiasis.
MECHANISM OFACTION:
 Acts on trophozoites.
 Has no effect on cysts.
 Nitro group of metronidazole is reduced by protozoan leading to cytotoxic
reduced product that binds to DNA and proteins resulting into parasite death.
 is active against the invasive form in gut and liver.
 The metronidazole metabolites are taken up into bacterial DNA, and form
unstable molecules. This function only occurs when metronidazole is partially
reduced. This reduction usually happens only in anaerobic cells

10. ORNIDAZOLE
USES:
It is used to treat people who have certain types of vaginal, urinary tract and
intestinal infections, or some specific infections that are in the body. These infections may be
caused by anaerobic bacteria (bacteria that do not use oxygen) or amoeba (single
celled parasites).
Adverse effects:
Dizziness, drowsiness or light-headedness in some
people, Nausea, Vomiting, Poor coordination, Skin
reactions and Taste disturbances.
N
N CH3
O2N
H2C CH CH2Cl
OH
1-chloro-3-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ol

11. SECNIDAZOLE
USES:
It Secnidazole is used to treat bacterial vaginosis (an infection caused by an overgrowth of
harmful bacteria in the vagina) in women. Secnidazole is in a class of medications called
nitroimidazole antimicrobials.
Adverse effects:
Vaginal itching or burning, redness or swelling or
white or yellow vaginal discharge (may be odorless).
N
N CH3
O2N
H2C CH CH3
OH
1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ol

12. EMETINE
USES:
Emetine is a drug used as both an anti-protozoal and to induce vomiting. It is produced from
the ipecac root. It takes its name from its emetic properties.
Adverse effects:
Heavy or over usage of emetine can carry the risk of
developing proximal myopathy and/or cardiomyopathy.
N
N
H
H
OCH 3
OCH 3
CH3
H
H
H3CO
H3CO
Emetine

13. DEHYDROEMETINE
USES:
Dehydroemetine is a synthetic derivative of emetine; used in the treatment of intestinal
amoebiasis.
Dehydroemetine is a pyridoisoquinoline which was developed in response to the
cardiovascular toxicity associated with emetine and results from the dehydrogenation of the
heterotricylic ring of emetine.
N
N
H
OCH 3
OCH 3
CH3
H3CO
H3CO
H
Dehydroemetine

14. DILOXANIDE FUROATE
Adverse effects:
It often causes flatulence and occasionally nausea, vomiting, diarrhea, urticaria, and pruritus.
N
O C
O
H3C Cl
Cl
O
O
4-[(dichloroacetyl)(methyl)amino]phenyl furan-2-carboxylate
Synthesis:
NH
OH
H3C
+ H
Cl
Cl
O
Cl
Chloral
4-(methylamino)phenol
+ NaCN
NaOH
N
OH
Cl
Cl
O
2,2-dichloro-N-(4-hydroxyphenyl)-N-methylacetamide
ClOC
O
Furoyl chloride
N
O C
O
H3C Cl
Cl
O
O
Diloxanide Furoate
NaOH
It shows a direct amoebicidal action against luminal
and it is active against non-invasive forms.

15. DILOXANIDE FUROATE MECHANISM OF ACTION
Unknown mechanism of action
This agent destroys the trophozoites of E. histolytica that eventually form into cysts. The
cysts are then excreted by persons infected with asymptomatic amebiasis.
USES:
Diloxanide furoate is a dichloroacetamide derivative that is a luminally active agent used to
eradicate cysts of E. histolytica in asymptomatic carriers and in those who have mild,
noninvasive disease, as well as after treatment with metronidazole in those who have
invasive amebiasis.

16. ANTI-PROTOZOAL DRUGS
GIARDIASIS
Giardiasis is an infection in your small intestine. It's caused by a microscopic parasite called
Giardia lamblia. Giardiasis spreads through contact with infected people. And you can
get giardiasis by eating contaminated food or drinking contaminated water. Pet dogs and cats
also frequently contract giardia.
Symptoms might include watery diarrhoea alternating with greasy stools. Fatigue, cramps and
belching wind may also occur. Some people have no symptoms.
Most cases clear up on their own within a few weeks. Severe cases are treated with antibiotics.
Drugs: Metronidazole, Nitazoxanide, Furazolidine
8-Hydroxy quinolines like iodochlorhydroxyquin(Clioquinol), Iodoquinol etc.

17. FURAZOLIDONE
O
O2N CH N N O
O
3-{[(5-nitrofuran-2-yl)methylidene]amino}-1,3-oxazolidin-2-one
USES:
Furazolidone is taken by mouth. It works inside the intestinal tract to treat cholera, colitis,
and/or diarrhea caused by bacteria, and giardiasis. This medicine is sometimes given
with other medicines for bacterial infections.
Adverse effects:
Lowered blood pressure, hives,
fever, joint pain, rash, stomach
upset, nausea, vomiting.

18. CLIOQUINOL
ADR:
Neuropathy and visual impairment.
8-HYDROXY QUINOLINES
IODOQUINOL
N
OH
I
I
Iodoquinol
N
OH
Cl
I
Clioquinol
N
OH
8-hydroxyquinoline
Clioquinol and iodoquinol are the halogenated derivatives of 8-
hydroxy quinolines, they are active against Entamoeba, Giardia,
Trichomonas and some fungi like Candida, Dermatophytes.
MOA:
Same as diloxanide furoate which kills the cyst forming TROPHOZITES in the intestine.

19. Trypanosomiasis
Human African trypanosomiasis, also known as sleeping sickness, is a vector-borne
parasitic disease. It is caused by infection with protozoan parasites belonging to the
genus Trypanosoma.
Trichomoniasis,
Also called trich, is a common sexually transmitted disease (STD). Trich is caused by a
tiny one-celled parasite named Trichomonas vaginalis. Anyone who's sexually active
can get it.
Drugs: Metronidazole, Diiodohydroxyquin(Iodoquinol), Quiniodochlor (Clioquinol),
Povidone-iodine

20. CLIOQUINOL
ADR:
Neuropathy and visual impairment.
8-HYDROXY QUINOLINES
IODOQUINOL
N
OH
I
I
Iodoquinol
N
OH
Cl
I
Clioquinol
N
OH
8-hydroxyquinoline
Clioquinol and iodoquinol are the halogenated derivatives of 8-
hydroxy quinolines, they are active against Entamoeba, Giardia,
Trichomonas and some fungi like Candida, Dermatophytes.
MOA:
Same as diloxanide furoate which kills the cyst forming TROPHOZITES in the intestine.

21. The disease like malaria, trypanosomiasis and leishmaniasis which are spread by
insect vectors, preventive measures is to use
 Insect repellent
 Insecticides
 Protective clothing etc.

22. LEISHMANIASIS (KALAAZAR)
Leishmaniasis is a parasitic disease that is found in parts of the tropics, subtropics,
and southern Europe. It is classified as a neglected tropical disease
(NTD). Leishmaniasis is caused by infection with Leishmania parasites, which are
spread by the bite of phlebotomine sand flies.
Drugs: Amphotericin B, Miltefosine, Sodium stibogluconate, Paromomycin

23. MILTEFOSINE
USES:
Miltefosine is a broad spectrum antimicrobial, anti-leishmanial, phospholipid drug that was
originally developed in the 1980s as an anti-cancer agent. It is currently the only
recognized oral agent used to treat visceral, cutaneous, and mucosal forms of
leishmaniasis, a neglected tropical disease.
Adverse effects:
Common side effects from miltefosine treatment
are nausea and vomiting, which occur in 60% of people. Other
common side effects are dizziness, headache, and daytime
sleepiness.
Serious side effects include rash, diarrhea, and arthritis.
O
P
O
N
+
O
O
-
14
Miltefosine

24. SODIUM STIBOGLUCONATE
USES:
Sodium stibogluconate is a medication used to treat cutaneous, visceral, and mucosal
leishmaniasis, a parasitic infection transmitted by sand-fly bites.
Adverse effects:
Sodium stibogluconate cause a reduced appetite,
metallic taste in mouth, nausea, vomiting, diarrhoea,
headache, tiredness, joint pains, muscle aches,
dizziness, and anaphylaxis.

25. PAROMOMYCIN
USES:
Paromomycin is an antimicrobial used to treat a number of parasitic infections including
amebiasis, giardiasis, leishmaniasis, and tapeworm infection. It is a first-line treatment for
amebiasis or giardiasis during pregnancy. Otherwise it is generally a second line treatment
option.
Adverse effects:
Abdominal cramps, diarrhea, heartburn, nausea,
and vomiting. Long-term use of paromomycin
increases the risk for bacterial or fungal infection.