This presentation provides a detailed exploration of malaria, a life-threatening disease caused by Plasmodium parasites, and the various antimalarial agents used to treat and prevent the disease. Covering key aspects like the types of malaria, transmission cycle, the role of antimalarial drugs, and emerging challenges like drug resistance, this PPT aims to provide valuable insights into the current landscape of malaria control. It also discusses the global impact of malaria, current preventive measures, drug-resistant strains, and innovative solutions for the future, including new drug development and malaria vaccines. Key Topics Covered: Introduction to Malaria: Definition, symptoms, and global impact Types of Malaria: Understanding the different Plasmodium species Transmission Cycle: Life cycle of the malaria parasite Antimalarial Agents: A deep dive into chloroquine, artemisinin-based combination therapies (ACTs), quinine, and newer drugs

1. By - Samruddhi S. Khonde
Asst. Prof
P. R. Patil Institute of Pharmacy,
Talegaon (S.P.)
Antimalarial
Agents

2. Antimalarial Agents
Malaria is a serious and sometimes fatal disease caused by parasites
belonging to the genus Plasmodium. It is transmitted to humans through the
bites of infected female Anopheles mosquitoes, which serve as the primary
vectors for the disease. Malaria is endemic in many tropical and subtropical
regions, affecting millions of people globally and leading to significant
morbidity and mortality, particularly among vulnerable populations such as
children under five and pregnant women. Despite advances in treatment and
prevention, malaria remains a major public health challenge, necessitating
ongoing efforts in research, surveillance, and control measures to combat its
spread and impact.

3. The Life Cycle of Malarial Parasites
The life cycle of Plasmodium, the causative agent of malaria, is complex and involves two
hosts: the female Anopheles mosquito and humans. This cycle can be divided into several key
stages:
1. Sporozoite Stage (Transmission)
•Infection of the Mosquito: The cycle begins when a female Anopheles mosquito bites an
infected human, ingesting blood containing Plasmodium gametocytes (the sexual form of the
parasite).
•Gametogenesis: Inside the mosquito's gut, the gametocytes develop into male and female
gametes, which fuse to form a zygote.
•Oocyst Formation: The zygote develops into an oocyst, which attaches to the gut wall of the
mosquito. Inside the oocyst, the parasite undergoes multiple divisions, producing thousands of
sporozoites.
•Release of Sporozoites: After a period of development, the oocyst bursts, releasing
sporozoites into the mosquito's hemolymph. These sporozoites migrate to the salivary glands of
the mosquito, ready for transmission.

4. Malarial Infection

5. The Life Cycle of Malarial Parasites
2. Human Infection (Sporozoite to Liver Stage)
•Inoculation: When the infected mosquito bites a human, it injects sporozoites into the bloodstream
through its saliva.
Liver Stage (Exoerythrocytic Cycle): The sporozoites travel to the liver, where they invade liver cells
(hepatocytes). Here, they undergo asexual reproduction, multiplying and developing into merozoites. This
stage lasts about 7-14 days, depending on the Plasmodium species.
3. Erythrocytic Cycle (Merozoite Stage)
•Release into Bloodstream: The liver cells eventually rupture, releasing thousands of merozoites into the
bloodstream.
•Invasion of Red Blood Cells: The merozoites invade red blood cells (RBCs), where they continue to
multiply asexually. Each infected RBC can produce more merozoites, leading to the rupture of the RBC
and the release of new merozoites into the bloodstream.
•Clinical Symptoms: This cycle of RBC invasion and rupture is responsible for the clinical symptoms of
malaria, including fever, chills, and anemia. The cycle can repeat every 48 to 72 hours, depending on
the Plasmodium species.

6. Malarial Infection

7. The Life Cycle of Malarial Parasites
4. Gametocyte Formation
•Development of Gametocytes: Some of the merozoites differentiate
into gametocytes (male and female forms) within the RBCs. These
gametocytes are crucial for the transmission of malaria back to the
mosquito.
5. Transmission Back to Mosquito
•Infection of the Mosquito: When another female Anopheles mosquito
bites an infected human, it ingests the gametocytes along with the blood.
This completes the cycle, allowing the gametocytes to develop into
gametes and restart the cycle in the mosquito.

8. Antimalarial Agents

9. Species of Malarial Parasites inside RBC
• Plasmodium
falciparum
• Plasmodium
vivax
• Plasmodium
malariae
• Plasmodium
ovale

10. Antimalarial Agents
Anti-Malarial Agents
Mechanism of
Action
Based on Chemical
Structure

11. Anti-Malarial Agents
Mechanism of Action
Blood Schizonticides
Chloroquine,
Quinine
Sulfate,
Amodiaquine,
Artesunate,
Artemether
Mefloquine,
Atovaquone,
Proguanil,
Pyrimethamine
Cycloguanil
pamoate
MOA-
Target the
asexual
blood stages
of the
parasite.
Gametocytocides
Primaquine
Phosphate,
pamaquine,
Artesunate
MOA-
Target the
sexual
stages of the
parasite to
prevent
transmissio
n.
Sporozoiticides
Primaquine
Phosphate,
pamaquine,
Proguanil,
Cycloguanil
pamoate
MOA-
Target the
liver stages
of the
parasite.

12. Antimalarial Agents
Classification based on Chemical Structure
Quinoline
Derivatives
1. 4-Aminoquinolines
Chloroquine
Amodiaquine
2. 8-Aminoquinolines
Primaquine phosphate
Pamaquine
3. Quinoline Methanol
Derivatives/Cinchona
alkaloids
Quinine sulfate
Mefloquine
Acridine
Derivative
Quinacrine
hydrochloride
Biguanides
(Dihydrofolate
Reductase
[DHFR]
Inhibitors)
Proguanil
Cycloguanil
pamoate (active
metabolite of
proguanil)
Diaminopyrimid
ine Derivatives
Pyrimethamine
Artemisinin
Derivatives
(Sesquiterpene
lactones with
an
endoperoxide
bridge)
Artesunate
Artemether
Hydroxy-
naphthoquinon
e Derivative
Atovaquone

13. Quinoline Derivatives

14. Antimalarial Agents
4-Aminoquinolines
 Chloroquine:
• Mechanism of Action: Inhibits the detoxification
of heme in the malaria parasite, leading to the
accumulation of toxic heme.
• Uses: Effective against uncomplicated malaria
caused by Plasmodium falciparum and
Plasmodium vivax. Also used for prophylaxis in
endemic areas.

15. Antimalarial Agents
Quinoline Derivatives
•Quinine:
• Mechanism of Action: Interferes with the parasite's ability
to digest hemoglobin.
• Uses: Used for severe malaria; can be administered orally
or intravenously.
• Side Effects: Can cause cinchonism (tinnitus, headache,
nausea).
•Mefloquine:
• Mechanism of Action: Similar to quinine, it disrupts the
parasite's metabolism.
• Uses: Used for prevention and treatment, especially in
chloroquine-resistant areas.
• Side Effects: Neuropsychiatric effects can occur; caution is
advised.
Mefloquine

16. Antimalarial Agents
8-Aminoquinolines
•Primaquine:
• Mechanism of Action: Generates
reactive oxygen species that damage the
parasite.
• Uses: Effective against the hypnozoite
stage of Plasmodium vivax and
Plasmodium ovale, preventing relapse.
Primaquine

18. The mechanism of action (MOA) of cinchona
alkaloids, particularly quinine and its derivatives,
primarily involves the following:
1.Inhibition of Hemozoin Formation: Quinine and other
cinchona alkaloids interfere with the malaria parasite's
ability to metabolize hemoglobin. They inhibit the
polymerization of heme into hemozoin, leading to the
accumulation of toxic free heme within the parasite.
2.Disruption of Parasite Metabolism: By accumulating
free heme, these drugs create a toxic environment for the
parasite, ultimately leading to its death.
3.Effects on Ion Channels: Some cinchona alkaloids, like
quinidine, also affect ion channels in the parasite, which
can disrupt its cellular functions.
CINCHONA ALKALOIDS
Quinoline Methanol Derivatives/Cinchona alkaloids

19. Antimalarial Agents
Artemisinin and its Derivatives
 Artemether:
• Mechanism of Action: Produces free radicals that
damage the parasite's proteins and membranes.
• Uses: Primarily used in combination therapies for severe
malaria, especially in cases of resistance to other drugs.
• Formulation: Available in oral and injectable forms.
 Artesunate :
• Mechanism of Action: Similar to artemether, it acts rapidly against the
malaria parasite.
• Uses: Administered intravenously for severe malaria; effective in
reducing mortality.
Artesunate

20. Antimalarial Agents
3. Antifolate Drugs/ Biguanides
(Dihydrofolate Reductase [DHFR]
Inhibitors)
 Pyrimethamine:
• Mechanism of Action: Inhibits
dihydrofolate reductase, disrupting
folate synthesis necessary for DNA
replication.
• Uses: Often used in combination with
sulfadoxine for treatment and
prophylaxis.
• Note: Can cause bone marrow
suppression; monitoring is required.
Pyrimethamine

21. Antimalarial Agents
• At C-4 position, the dialkylaminoalkyl side chain has 2-5 carbon
atoms between the nitrogen atoms, particularly the 4-
diethylaminomethyl butyl amino side chain that is optimal for
activity, as in chloroquine and quinacrine.
• The substitution of a hydroxyl group on one of the ethyl groups on
the tertiary amine (hydroxy quinoline), reduces toxicity.
• Incorporation of an aromatic ring in the side chain (e.g.
amodiaquine) gives a compound with reduced toxicity and activity.
• The tertiary amine in the side chain is important.
• The introduction of an unsaturated bond in the side chain was not
detrimental to activity.
• The 7-chloro group in the quinoline nucleus is optimal, the methyl
group in position 3 reduces activity, and an additional methyl
group in position 8 abolishes activity.
• The D-isomer of chloroquine is less toxic than its L-isomer
Structure Activity of Relationship
Structure of Quinine

22. Thank You