Amoebicidal drugs eradicate the parasitic species of amebae in animals or humans. Classification, Chemistry, Mode of action, Side effects....

1. • Mr. Hitesh Vishwanath Shahare
• Assistant Professor
• Dept. Ph.’ Chem.
• SNJBs Shriman Sureshdada Jain Coll. Ph. Chandwad
ANTIIAMOEBIC
DRUGS

2. Learners will be able to know;
1. Introduction
2. Classification
3. SAR & MOA
4. Marketed Preparations
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3. Protozoal Infection
Unicellular protozoal cells have metabolic processes closer to human
cells than bacteria
Protozoal infections are less easily treated than bacterial infections:
Protozoal
Infections
Malaria
Amoebiasis
Leishmaniasis
Trypanosomiasis
Trichomoniasis
Giardiasis

4. Amoebiasis
 Causative agent: Protozoal parasite
 Amoebiasis: Infection of Large Intestine
: Entamoeba
histolytica
Cyst Tropozoites
- Not active
- Survive outside
of Host Body
-Tissue lysis of wall of intestine
Diarrhoea
Dysentery
-Presence of Blood
& mucous in stools
-Abdominal Pain
Parasite invade to blood vessels & Causes problems
in Liver & Brain: Leads to death of Host
Exist in 2 Forms

5. Life Cycle of
Amoeba
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6. Classification
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7. Chemical Classification
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8. Nitroimidazole derivatives
2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethanol
Metronidazole
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9. Binds to proteins and DNA, resulting in cell death
Metronidazole is a Prodrug that is reduced in the cytoplasm
by a Nitroreductase enzyme; resulting toxic intermediates
disrupt nucleic acid structure.
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10. Metabolism: In the liver, metabolism of metronidazole leads to two
major metabolites, hydroxylation of the 2-methyl group to 2-
hydroxymethyl metronidazole and oxidation to metronidazole acetic
acid (MAA)
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11. Side effects
Uses
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12. Synthesis of Metronidazole
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13.  Mechanism of action is similar to that of Metronidazole
 Used in the treatment of intestinal and hepatic Amoebiasis
 Greater efficacy than Metronidazole
.
Tinidazole
1-Chloro-3-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ol
Ornidazole
1-(2-ethylsulfonylethyl)-2-methyl-5-nitro-imidazole

14. Dichloroacetamide Derivatives
 Mechanism of Action:
 Side effects: Flatulence, Vomitting
 Effective in Intestinal, Luminal and local Amoebiasis
Diloxanide Furoate
4-[(Dichloroacetyl)(methyl)amino]phenyl furan-2-carboxylateDiloxanide

15. 2,2-Dichloro-N-[[4-[[(2,2-dichloroacetyl)-(2-
ethoxyethyl)amino]methyl]phenyl]methyl]-N-(2-
ethoxyethyl)acetamide
2,2-dichloro-N-(2-ethoxyethyl)-N- [4-(4-
nitrophenoxy)benzyl]acetamide
Teclozan
Etofamide
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16. Alkaloids
Emetine
Dehydroemetine
 Differ only in a double bond next to the ethyl substituent
Alkaloid derived from Cephaelis ipecacuanha
Synthetic analog
Less side effects
 Parenterally administered (IM/SC), by oral route cause vomiting
 MOA: Inhibiting intra-ribosomal translocation of tRNA-amino acid complex →
Inhibition of Protein Synthesis

17. 1. Emetine Possesses a skeleton with two Tetrahydoisoquinoloine ring
system and a Terpenoidal portion.
2. Psychotrine is a phenolic. It gives Emetine on reduction followed by
methylation.
3. Emetine is non Phenolic moiety.
4. N-5 and C-9 are critical positions : Essential for Biological activities
Chemistry
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18. 1. Local stimulation: Pain and tenderness in the area of injection
2. Gastrointestinal tract discomfort: Nausea, vomiting– CTZ (oral and IV)
3. Diarrhoea and abdominal cramps
4. Neuromuscular blockade: Muscle weakness and discomfort
5. Cardiac toxicity: Arrhythmias, congestive heart failure, hypotension,
ECG changes
Contraindication: Not be used in patients with cardiac or renal disease,
in pregnancy
Emetine Adverse Effects

19. 8-Hydroxyquinolines
 Quinoline ring: Basic nucleus
 Effectiveness limited to bowel luminal organism
-Not effective against intestinal wall/extraintestinal tissue tropozoites
 Poor Absorption
 Interfere with Thyroid functions: decreases 131I uptake
 SE: On long term use-Goiter
Neurotoxicity
Green stools
5-Chloro-7-iodo-quinolin-8-ol
5,7-diiodoquinolin-8-ol
Iodoquinol Clioquinol

20.  Broad-spectrum Antiparasitic and Antiviral drug used in medicine for the
treatment of various helminthic, protozoal and viral infections.
 SE: Stomach pain, headache, vomiting, discolored urine, excessive
urinating, skin rash, itching
 MOA: Interference with the Pyruvate: Ferredoxin oxidoreductase (PFOR)
enzyme-dependent electron transfer reaction which is essential to anaerobic
energy metabolism
 Tizoxanide is an active metabolite of Nitazoxanide
Nitrothiazolidines
Nitazoxanide
[2-[(5-Nitro-1,3-thiazol-2-yl)carbamoyl]phenyl]ethanoate

21. (RS)-N'-(7-chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine
Chloroquine
 Effective in tissue or hepatic Amoebiasis
 Very effective in combination with Dehydroemetine or Emetine in
amebic liver abscess
4-Aminoquionolines

22. Antibiotics
Paromomycin
 Aminoglycoside antibiotic
 Use in Amoebiasis, Leishmaniasis
 MOA: Cause leakage in cell membrane of parasite
 SE: Abdominal distress and Diarrhea
 Administered as by IM and in capsule dosage form
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23. Marketed Preparations
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25. 2525
shahare.hvcop@snjb.org
Thank You!
SNJBs Shriman Sureshdada Jain Coll. Ph. Chandwad