Antimalarial agents are chemotherapeutic agents used to prevent and treat malaria caused by protozoan parasites of the genus Plasmodium. There are four main species that cause human malaria: P. malariae, P. vivax, P. falciparum, and P. ovale. Common antimalarial classes include 4-aminoquinolines like chloroquine, quinoline-methanols like mefloquine, cinchona alkaloids like quinine, and diaminopyrimidines like pyrimethamine. These work by accumulating in the parasite and raising vesicular pH to interfere with hemoglobin degradation or through other mechanisms like oxidative damage. Artemisinins

1. Antimalarial agents
Prepared By Ganesh D.Mote
AGCOP,Satara

2. Antimalarial Agents
• Defination-Antimalarials are chemotherapeutic agents which are
used for the prevention and treatment of malaria.
• The causal organisms responsible for malaria belong to the genus plasmodium
which is of the
• class of protozoa known as sporozoa. There are four different species which are
accepted as being responsible for human malaria. These are Plasmodium
malariae, the parasite of quartan malaria.
• Plasmodium vivax, the parasite of benign tertian malaria.
• Plasmodium falciparum, the parasite of malignant or subtertian malaria.
• Plasmodium ovale, the parasite that causes a mild type of tertian malaria

3. Life cycle of malarial parasite.

4. Classification
1. 4-Aminoquinolines : Chloroquine, Amodiaquine,Piperaquine.
2. Quinoline-methanol : Mefloquine.
3. Cinchona alkaloid : Quinine, Quinidine.
4. Biguanide : Proguanil (Chloroguanide), Chlorproguanil.
5. Diaminopyrimidine : Pyrimethamine.
6. 8-Aminoquinolines : Primaquine, Bulaquine.
7. Sulfonamides and sulfone-
Sulfadoxine,Sulfamethopyrazine,Dapsone.
8. Tetracyclines : Tetracycline, Doxycycline.
9. Sesquiterpine lactones : Artesunate, Artemether,Arteether.
10. Amino alcohols : Halofantrine, Lumefantrine.
11. Mannich base : Pyronaridine
12. Naphthoquinone : Atovaquone.

5. 1.
4-Aminoquinoline Analogues
CHLOROQUINE

6. 2. Quinoline-methanol
N
OH
CF3
F3C
CH NH
(2,8-bis(trifluoromethyl)quinolin-4-yl)(piperidin-2-yl)methanol
Mefloquin

7. 3.Cinchona alkaloid

8. 4.Biguanide
1-(p-Chlorophenyl)-5-isopropylbiguanide hydrochloride
N
H
NH
N
H
NH
N
H
ClH
Cl
Proguanil

9. 5.Diaminopyrimidine
2, 4-Diamino-5-(p-chlorophenyl)-6-ethylpyrimidine
N
N
Cl
NH2H2N
Pyrimethamine

10. 6.
8-Aminoquinolines

11. 7.Sulfonamides and sulfone-
[4, 4 Sulfonyldianiline}
S
O
O
H2N NH2
Dapsone

12. 8. Tetracyclines

13. 9.Sesquiterpine lactones

14. 10.Amino alcohols

15. 12.Naphthoquinone

16. MOA of Chloroquine
• Uses of Chloroquin-
• Chloroquine is the drug of choice for clinical cure and suppressive prophylaxis of all types of
malaria,
• except that caused by resistant P. falciparum.
• Uncomplicated cases are treated orally, while i.v. chloroquine is rarely employed for complicated/
cerebral malaria in adults.
Heme itself or its complex with chloroquine then damages the plasmodial membranes
Polymerization of toxic haeme to nontoxic parasite pigment hemozoin is inhibited by formation of
chloroquine-heme complex
Chloroquine-It is actively concentrated by sensitive intraerythrocytic plasmodia.higher concentrationis found
in infected RBCs. By accumulating in the acidic vesicles of the parasite and because of its weakly basic nature,
it raises the vesicular pH and thereby interferes with degradation of haemoglobin by parasitic lysosomes.

17. MOA of 8-Amino quinoline(Primaquine)
Step-1
• primaquine can generate ROS via an autoxidation
of the 8-amino group. The formation of a radical
anion at the 8-amino group
Step-2
• As a result, cell -destructive oxidants, such as
hydrogen peroxide, superoxide, and hydroxyl
radical, can be formed.
Step-3
• leading to oxidative damage to critical cellular
components.

18. Mechanism of action artemisinin
inhibits protein synthesis and ultimately results in
lysis of the parasite
Iron-mediated cleavage of the bridge releases a highly reactive
free radicals species that binds to membrane proteins,
causes lipid peroxidation, damages endoplasmic reticulum.
The endoperoxide bridge in its molecule appears to
interact with haeme in the parasite.

19. Chloroquine synthesis

20. Chloroquin synthesis(Cont….)