Antiprotozoal Drugs- Medicinal Chemistry-Pharmacy- As per PCI Syllabus- Lecture Notes

1. Anti Protozoal Drugs
Dr. Akhil Nagar
RCP-IPER
Shirpur

2. Anti Protozoal Drugs
• Protozoan infections are parasitic diseases caused by
organisms formerly classified in the
Kingdom Protozoa.
• They are usually contracted by either an insect vector
or by contact with an infected substance or surface
and include organisms called Amoebozoa.
• Protozoan infections are responsible for diseases that
affect many different types of organisms. Many of the
most prevalent and deadly human diseases are caused
by a protozoan infection, including African Sleeping
Sickness, amoebic dysentery, and malaria.

3. • The species originally termed "protozoa" are not closely
related to each other and only have superficial similarities.
• In some areas with temperate climates in which sanitation is
poor, the prevalence of amebiasis has been estimated to be as
high as 20% of the population.
• The causative organism, Entamoeba histolytica, can invade
the wall of the colon or other parts of the body.
• Antiprotozoal agents is a class of pharmaceuticals used in
treatment of protozoan infection.
• Common protozas are Trypanosoma which is
a genus of kinetoplastids.
• African trypanosomiasis, also known as African sleeping
sickness or simply sleeping sickness, is an insect-
borne parasitic disease.

4. • The Amebicides that are effective against both intestinal
and extraintestinal forms of the disease.
• Group-1: Alkaloids emetine and dehydroemetine, the
nitroimidazole derivative metronidazole, and the
antimalarial agent chloroquine and Atovaquone
• Group-2: amebicides that are effective only against
intestinal forms of the disease includes the
aminoglycoside antibiotic paromomycin, 8-
hydroxyquinoline derivative iodoquinol and diloxanide.
• Other than Trypanosoma, Leishmaniasis is a chronic
tropical disease caused by various flagellate protozoa of
the genus Leishmania.
• The more common visceral form caused by Leishmania
donovani, called kala-azar.

5. Metronidazole
Tinidazole,
Ornidazole
2-Methyl-5-nitroimidazole-1-ethanol

6. • Nitoimidazole Derivatives:
• It is effective against Gram-positive anaerobic bacilli. It is also
effective against Gram-positive anaerobic bacilli, bactericidal in
action.
• Reactive intermediate formed in the microbial reduction of the
5-nitro group of metronidazole covalently binds to the DNA of
the microorganism
• Potential reactive intermediates include the nitroxide, nitroso,
hydroxylamine, and amine.
• Metronidazole acts as an artificial electron acceptor after
accumulating with in cell as reduced comp.
• Nitro group accepts the proton and divert the normal pathway.
• The electron sources can be NADH or sulfide bonds.
• Metronidazole and other derivatives can also cause loss of
helical structure of DNA.

7. Diloxanide
Iodoquinol
Pentamidine

8. • DILOXANIDE:
• Its an ester of 2,2-dichloro methylacetanilide, with the
discovery of dichloroacetamides which possessed
amebicidal activity.
• Drug metabolism studies indicate that hydrolysis of the
amide is required for the amebicidal effect.
• Nonpolar esters of diloxanide are more potent than polar
ones.
• IODOQUINOL:
• 5,7-Diiodo-8-quinolinol microcrystalline, light-sensitive
substance.

9. • Pentamidine Isethionate:
• The principal use of pentamidine is for the treatment of
pneumonia.
• Pentamidine has been used for the prophylaxis and
treatment of African trypanosomiasis. It also has some
value for treating visceral leishmaniasis.
• Atovaquone: 1,4-naphthoquinone, highly lipophilic,
water-insoluble, an essential component of the
mitochondrial electron transport chain in microorganisms.
• They interfere with the function of electron transport
enzymes.
• Eflornithine:
• Eflornithine is a myelosuppressive drug that causes high
incidences of anemia, leukopenia, and thrombocytopenia.

10. • The irreversible inactivation of ornithine decarboxylase
by eflornithine is accompanied by decarboxylation and
release of fluoride ion from the inhibitor.
• Eflornithine is supplied as the hydrochloride salt. It may
be administered either intravenously or orally.
Approximately 80% of the unchanged drug is excreted in
the urine.
Isethionates are esters of long-chain aliphatic carboxylic
acids (C8 – C18) with isethionic acid (2-hydroxyethanesulfonic
acid) or salts thereof, such as ammonium isethionate or sodium
isethionate. They are also referred to as acyl isethionates or
acyloxyethanesulfonates.

11. Atovaquone Eflornithine