This slide contain information about Anti Malarial Drugs and their description with the synthesis of Chloroquine and pamaquine SAR of quinolines Miscellaneous agents of anti Malarial

1. ANTI MALARIAL DRUGS
PREPARED BY:-
PRANJAL SAXENA
B.PHARMACY 6TH SEM.
ORIENTAL UNIVERSITY INDORE

2. INTRODUCTION:-
MALARIA:-
A disease caused by a plasmodium parasite, transmitted by the bite of
infected mosquitoe.
The word Malaria Originated fromItalian terminology:
Mal+ aria.. Means Bad Air, because protozoa of the Plasmodium
species are transmitted by mosquitoes.
Anti malarial drugs are the drugs which are used in the treatment of
Malaria.

3. ETIOLOGY OF MALARIA:-
Obligate intracellular Blood born parasite.
MALARIA is caused by four Species:-
A. Plasmodium Vivax
B. Plasmodium Falciparum
C. Plasmodium Ovale
D. Plasmodium Malariae

4. ETIOLOGY OF MALARIA:-
Three of which are produce mild form of Malaria by
destroying RBC and produce Anaemia.
The most Dangerous species is Plasmodium Falciparum
It cause infection in RBC and RBCs becomes sticky and
forms lumps in the capillaries which causes Circulatory
Arrest.
This Disease is responsible for many deaths every year.

5. CLASSIFICATION OF ANTIMALARIAL DRUGS:
-
There are Various drugs are used in treatment of Malaria:-
Cinchona Alkaloids
4 Amino Quinolines
8 Amino Quinolines
Acridine Derivatives
Antifolates
Sulphonamides
Miscellaneous

6. Cinchona Alkaloids:-
[R]
Quinoline
Cinconine
Cinconidine
Quinidine

7. 4 Amino Quinolines:-
Santoquine
Hydrochloroquine

8. 8- Amino Quinolines:-
[R]
Primaquine.
Pamaquine
Isopentaquine

9. Acridine Derivatives:-
[R]
Quinacrine
Acriquine

10. Antifolates:-
BIGUANIDES:-
R R1
Proguanil Cl. H
Chloroguanil Cl. Cl
Bromoguanil Br. H

11. Antifolates:-
Diaminopyrimidine
A. Pyrimethamine
Trimethoprim

12. Sulphonamides:-
Sulphadoxine
Sulphadiazine

13. Miscellaneous:-
Dapsone
Artemether

14. Mode of Action:-
1.
2.
3.
3 different mechanism of action are suggested for these drugs:-
DNA interaction
Ferriprotoporphyrin
Weak Base hypothesis
DNA INTERACTION:- Drugs get intercalated into DNA of the parasite, so
DNA stopped which inhibit plasmodium parasite.
FERRIPROTOPORPHYRIN:- The plasmodium parasite utilities host
Heamoglobin as a source of amino acid. Where haemoglobin convert or
release as ferriprotoporphyrin which is very much toxic products called
HAEMOZOIN( MALARIAL PIGMENT).

15. The steps involved in the conversion of ferriprotoporphyrin to
HAEMOZOIN is inhibited by drugs eg. Chloroquine.
WEAK BASE HYPOHESIS :- The Drug which are weak Base they
acuumulate in a location which is acidic, The exmacellular fluid
af parasite at pH7.4 , The weak Base will moves towards more
acidic pH at lysosine. Once the Acid base reaction Occurs it
elevates the pH in lysosine and reduce the ability of parasite to
digest the Host Haemoglobin and inturn get inhibited.

16. Synthesis of chloroquine:-
STEP 1

17. STEP 2
STEP 3

18. Properties and Uses:-
Chloroquine exist as a white or almost white crystalline powder.
Soluble in water and ethanol.
Very slight soluble in ethanol.
Mainly used as an ANTIMALARIAL.
Also used in anti histaminic and anti inflammatory agents.
Adverse reactions of drug include Retinopathy, hemolysis in patients, weakness,
impaired liver function.
DOSAGE FORM:-
Chloroquine sulphate Injection I.P., B.P.
Chloroquine sulphate tablet IP and B.P.

19. SAR OF QUINOLINES:-
C4 position of Dialkyl amino side chain is optimal for the activity.
The substitution of hydroxyl groups on one of the ethyl group of
territory amine reduce toxicity.
The territory amine in side chain is important.
Introduction of chloro group at 7 position is optimal for activity.
Introduction of unsaturated bond in side chain was not detrimental to
activity.
The d isomers of chloroquine is less toxic than its l isomers.

20. 1.
2.
In corporation of aromatic ring in the side chain gives a compound with reduce toxicity
and activity.
Methyl group at 3- position reduce the activity and additional methyl group in position 8
abolish the activity.
SAR OF CHINCONA ALKALOIDS:-
Modification of secondary alcohol at C9 position results in deminishing the activity.
The configuration at position 8&9 affect the juxtaposition of OH group.

21. 5
3. presence of methoxy group in quinine is not important
4. Introductionn of halogen group at C 8 position enhance activity.
Replacementt of methoxy group by Halogen specially Cl enhances activity.
PROPERTIES AND USES:-
Quinine HCL exist as a fine, silky colour less
Soluble in water and in alcohol
Used in treatment of Malaria.

22. Synthesis of Pamaquine:-

23. SAR OF QUINACRINE HCL
Acridine ring considered to have antibacterial antimicrobial activity.
When methoxy group at position 2 at Cl at position 6 the compound becomes
antimalarial.
Quinacrine was the first synthetic agent that wad used before Quinolines.
Methoxy group is replaced by OC2H5 toxicity increases.
If Cl is replaced by other halogen again the antimalarial activity decreases .
Side chain of 2 aminob5 diethyl amino pentane has no anti malarial activity.

24. But when attach to this aromatic system the compound
becomes Anti Malarial.
When at position 1 nitrogen is introduced it becomes azacrine
which has very good antimalarial activity and rapid onset of
action.
PROPERTIES AND USES:-
Now it is not used as antimalarial agents.
Used as shizontocidal.

25. ARTEMETHER:-
METABOLISM
Drug is metabolised by dialkylization by CYP3A4.
PROPERTIES AND USES:-
Practically insoluble in water and soluble in Methanol.
Specially used in treatment of Malaria against PLASMODIUM
FALCIPARUM by inhibiting Nucleic acid and protein synthesis.

26. ARTISUNATE:-
METABOLISM:-
Rapidly metabolised to DNA which is further metabllise by
glucoranadition in liver .
The metabolite excreted from urine.
PROPERTIES AND USES:-
Whtie crystalline powder
Active against PLASMODIUM FALCIPARUM
Insoluble in water and soluble in ethanol.

27. THANK YOU