Malaria – Basic Knowledge about Antimalarial Drugs

Malaria is an infectious disease caused by Plasmodium parasites, transmitted through the bite of Anopheles mosquitoes. Malaria treatment primarily relies on using antimalarial drugs. Below is some basic knowledge about antimalarial drugs, based on the questions you provided:

I. Antimalarial Drugs:

1. Antimalarial drugs for chloroquine-resistant strains:

• 4-aminoquinoline dimer derivatives:

• Piperaquin is a dimer derivative of 4-aminoquinoline, effective against chloroquine-resistant strains.

• Structure-Activity Relationship (SAR) studies on the chloroquine structure with R = (CH2)n-N <, n = 3-5, – N< (tertiary, secondary, primary or heterocyclic).

• The method to create derivatives effective against chloroquine-resistant strains is to create dimer derivatives and shorten the hydrocarbon chain with other hydrophobic groups.

• Note: SAR is the study of the relationship between the structure and activity of compounds. Changing the structure of chloroquine, such as replacing the chloro group with other hydrophobic substituents, extending or shortening the hydrocarbon chain at the R = (CH2)n-N < position, or modifying the – N< position to increase the derivative’s solubility, can create new derivatives more effective against chloroquine-resistant strains.

2. Drugs acting on Plasmodium through antifolinic or dihydrofolate reductase (DHFR) inhibition:

• Proguanil is a prodrug metabolized in the body into an active metabolite that inhibits DHFR in Plasmodium.

3. Thaleoquinin reaction is characteristic of:

• Methoxy group at R1: The Thaleoquinin reaction is characteristic of the methoxy group at the R1 position in the quinine structure.

4. The binding ability between pyrimethamine and the enzyme Plasmodium falciparum dihydrofolate reductase (PfDHFR). S108N means:

• Point mutation at Serine 108: S108N is a mutation variant on the gene encoding PfDHFR, replacing Serine at position 108 with Asparagine.

5. Chloroquine is the ‘gold standard’ in malaria treatment and has the structure of:

• 4-aminoquinoline: Chloroquine is an antimalarial drug with a 4-aminoquinoline structure.

6. Quinin can be quantified using UV spectrophotometry due to the:

• Quinolone ring: The quinolone ring in the Quinin structure creates UV absorption at a characteristic wavelength, allowing for quantification using UV spectrophotometry.

7. Water-soluble and stable artemisinin derivatives can be used for injection/H2O:

• Artelinic acid: Artelinic acid is an artemisinin derivative that is water-soluble and stable, allowing for intravenous administration.

8. The chosen position for modification to create more potent artemisinin derivatives:

• Carbonyl group at position E: Modifying the carbonyl group at position E in the artemisinin structure can create derivatives with stronger antimalarial activity.

9. Which of the following drugs is preferred for malaria prophylaxis in the community?

• Proguanil: Proguanil is the recommended antimalarial prophylactic drug for the community due to its safety and efficacy.

10. Besides synergizing with proguanil, atovaquone also synergizes with:

• Chlorproguanil: Atovaquone is an antimalarial drug that synergizes with both proguanil and chlorproguanil.

11. Chloroquine belongs to the structural group of:

• 4-Aminoquinoline: Chloroquine belongs to the group of antimalarial drugs with a 4-aminoquinoline structure.

12. Chloroquine resistance: a point mutation at K76T on the chloroquine resistance transporter (CRT) pump affects:

• Loss of positive charge at the CRT pump and the transport of dicationic chloroquine out of the parasite’s cytoplasm: The K76T mutation on the chloroquine resistance transporter (CRT) pump causes the loss of positive charge, pushing dicationic chloroquine (the active form) out of the parasite’s cytoplasm, leading to drug resistance.

13. The PfDHFR S108N resistance variant causes the loss of pyrimethamine’s activity by:

• Spatial hindrance at the binding site, preventing pyrimethamine from binding to the mutated PfDHFR: The S108N mutation on PfDHFR creates a structural change that hinders pyrimethamine from binding to the enzyme, resulting in the loss of drug activity.

14. Mefloquin belongs to the structural group of:

• 4-Quinoleinyl methanol: Mefloquin is an antimalarial drug with a 4-quinoleinyl methanol structure.

15. Given the Mefloquin structure, how many hydrogen bond acceptor groups does it have at most?

• 3: The structure of Mefloquin has a maximum of 3 hydrogen bond acceptor groups.

16. Sulfadoxin is a malaria treatment drug that acts by:

• Inhibiting dihydropteroate synthetase: Sulfadoxin is an antimalarial drug that inhibits the dihydropteroate synthetase enzyme of Plasmodium.

17. The following statement is not consistent with the atovaquone structure:

• The structure shows a small logP value: Atovaquone is an antimalarial drug with a lipophilic (fat-soluble) nature. The logP value reflects the lipophilicity of a compound; the higher the logP, the more lipophilic the compound is. Therefore, the structure of atovaquone shows a large logP value, not a small one.

18. Among the following antimalarial drugs, which one is derived from sulfonamide?

• Fansidar: Fansidar is a combination of two drugs: sulfadoxin and pyrimethamine. Sulfadoxin is a sulfonamide derivative.

19. Mefloquin is an antimalarial drug with the structure of:

• 4-Quinoline methanol derivative: Mefloquin is a derivative of 4-quinoline methanol.

20. Artemisinin can be quantified using UV spectrophotometry through which transformation?

• Conversion to Q292 derivative / alkali, followed by Q260 / acid: Artemisinin can be quantified using UV spectrophotometry by converting it to the Q292 derivative in an alkaline medium, followed by conversion to the Q260 derivative in an acidic medium.

21. Artemisinin is a good antimalarial treatment, but it has a significant drawback:

• Rapid relapse: Artemisinin is an effective antimalarial drug, but it has a drawback of being prone to relapse.

22. Among the following antimalarial drugs, which one is water-soluble and used for injection?

• Artesunate: Artesunate is an artemisinin derivative that is water-soluble and used for intravenous administration.

23. The structure of the drug believed to restore chloroquine’s antimalarial activity on the K76T chloroquine resistance transporter (CRT) pump is due to:

• Maintaining a positive charge at the CRT pump and keeping dicationic chloroquine in the digestive vacuole: Drugs believed to restore chloroquine’s antimalarial activity on the K76T chloroquine resistance transporter (CRT) pump typically have a structure that creates a positive charge at the CRT pump, helping to keep dicationic chloroquine (the active form) in the digestive vacuole, preventing it from being pushed out of the parasite’s cytoplasm.

24. Antimalarial prophylaxis drug?

• Proguanil: Proguanil is the recommended drug for malaria prophylaxis.

25. What is the R group in sodium artesunate?

• -CHOCH2CH2COONa: Sodium artesunate is an artemisinin derivative with an R group of -CHOCH2CH2COONa.

26. Chloroquine-resistant malaria parasites have a K76T mutation on the chloroquine resistance transporter (CRT) pump. What does K76T mean?

• Point mutation on Lysine (K) 76 to Threonine (T): K76T is a point mutation that replaces Lysine at position 76 with Threonine on the chloroquine resistance transporter (CRT) pump.

27. The resistance variant of the Plasmodium falciparum dihydrofolate reductase (PfDHFR) enzyme S108N inactivates the binding ability to pyrimethamine. What does S108N mean?

• Point mutation at Serine 108 to Asparagine: S108N is a point mutation that replaces Serine at position 108 with Asparagine on the PfDHFR enzyme.

Note:

• Information about antimalarial drugs needs to be updated regularly due to the emergence of new drug-resistant parasite strains.

• Use antimalarial drugs as directed by a doctor.

• Prevent malaria by sleeping under a mosquito net, using insect repellent, and avoiding mosquito exposure at night.

Hopefully, this information is helpful to you.