THIS PRESENTATION ABOUT ANTIMALARIAL DRUGS DETAILING THE COMPLETE INFORMATION ABOUT THE DRUGS USED WITH ITS MECHANISM OF ACTION, STRUCTURAL ACTIVITY AND DOSES.

1. Nature Products as leads for new pharmaceuticals

3. M A L A R I A
Malaria is a infectious disease caused by parasite called as Plasmodium.
This parasites spend an asexual phase in a man and a sexual phase in female
Anaphiles mosquito.
Plasmodium falceparum
Plasmodium malariae
Plasmodium ovale
Plasmodium vivax

4. Fig :- Malarial life cycle

5. CLASSIFICATION BASED ON CHEMICAL STRUCTURE
1) Quinolines
 Cinchona alkaloids
 4-aminoquinolines
 8-amionquinolines
2) 9-aminoacridines
3) 2,4-diaminopyrimidines
4) Biguanides
5) Sulfones and sulfonamides
6) Miscelleneous agents

6. A ) 4 -A M I N O Q U I N O L I N E S
IUPAC NAME :- Quinolin-4-amine
 4-Aminoquinoline is contain amino group at the 4-position of the quinoline
 4-aminoquinoline are antimalarial agents useful in treating erythrocytic plasmodial
infections
 Quinoline nucleus is essential for antimalerial activity as it can direct the intercalate
into plasmodium DNA.
In this drugs replacement of methoxy group with halo substituent's improve the
activity of drug molecule.
Examples:- amodiaquine, Chloroquine, and hydroxychloroquine

7. 4 - a m i n o q u i n o l i n e s

8. Chloroquine
IUPAC name:- 4-[(7-Chloro-2-methoxy-pyrido[3,2-b]
quinolin-10-yl)amino]-2,6-bis(pyrrolidin-1-ylmethyl)
phenol
4 - a m i n o q u e n o l i n e s
IUPAC NAME :- Quinolin-4-amine

9. 4 -A M I N O Q U E N O L I N E S

10. Hydroxychloroquine
IUPAC name:- (RS)-2-[{4-[(7-chloroquinolin-4-yl)amino]
pentyl}(ethyl)amino]ethanol
IUPAC NAME :- Quinolin-4-amine
4 - a m i n o q u e n o l i n e s

11. Amodiaquine
IUPAC name :- 4-[(7-chloroquinolin-4-yl)amino]-2
-[(diethylamino)methyl]phenol
4 - a m i n o q u e n o l i n e s
IUPAC NAME :- Quinolin-4-amine

12. Pyronaridine
IUPAC name :- 4-[(7-Chloro-2-methoxy-pyrido[3,2- b]quinolin-10-yl)
amino]-2,6- bis(pyrrolidin-1-ylmethyl)phenol
4 - a m i n o q u e n o l i n e s
IUPAC NAME :- Quinolin-4-amine

13.  SAR
• The presence of quinoline nucleus along with chloro substituent at C7 positio
n and Amino alkyl side chain at C4 position is essential for antimalerial activ
ity
• The substitution of addition aromatic ring in quinoline nucleus reduce drug p
otential.
• In side chain a carbon chain should be consist of 4-6 carbon atom is essential
for optimum activity.
• In side chain ( at C4 position) terminoamine function should be tertiary as it
produced the effective binding with receptor.
• Substitution of hydroxyl group at ethyl group of terminal amine then it
reduced the toxicity and thus increase plasma concentration of drug.
• Introduction of aromatic nucleus in side chain reduced the toxicity as well as
the activity.
• Introduction of unsaturation in side chain does not interfere with the activity
of drug molecule.

14. B ) 8 -A M I N O Q U I N O L I N E S
IUPAC name :- Quinolin-8-amine
• 8-Aminoquinoline is a form of aminoquinoline with an amine at the 8-position of quinoline
• The 8-aminoquinoline family of drugs contains three
members, primaquine, tafenoquine and pamaquine and are used in the treatment of malaria. They may be
used to eradicate malaria hypnozoites from the liver and have both been use malaria for prophylaxis
The 8-aminoquinoline drugs must not be given to patients with G6PD deficiency, because they cause
potentially fatal haemolysis in these patients

15. Primaquine
IUPAC name :- (RS)-N-(6-methoxyquinolin-8-yl)pentane-1,
4-diamine
IUPAC name :- Quinolin-8-amine
8 -A M I N O Q U I N O L I N E S

16. Tafenoquine
IUPAC name :-N-[2,6-Dimethoxy-4-methyl-5-[3-(trifluorom
ethyl)phenoxy]quinolin-8-yl]pentane-1,4-diamine
IUPAC name :- Quinolin-8-amine
8 -A M I N O Q U I N O L I N E S

17. Pamaquine
IUPAC name :- N,N-diethyl-N'-(6-methoxyquinolin-8-yl)pentane
-1,4-diamine
IUPAC name :- Quinolin-8-amine
8 -A M I N O Q U I N O L I N E S

18. MODE OF ACTION
 Its mode of action is not so clear but it claim to causes a destruction or
breakdown of parasitic mitochondria as well as it undergoes a
intercalation into DNA structure and thus inhibit the gamatocytic and
exoerythrocytic form of malarial parasite

19. SAR:
• A presence of phenoline nucleus along with the presence of
methoxy group with C6 position and amino alkyl position at C8
position is essential for the anti malarial activity
• The presence of methoxy at C2 or C4 position instead of C6
position does not affect the activity of drug molecule.
• Introduction of additional methoxy function at C2 position
increase the therapeutic index of drug molecule.
• Substitution of additional ring in quinoline structure reduce
activity of drug molecule.
• In side chain, a carbon chain between two amino function should
be consist of 4-6 carbon atoms as it is essential to express a
optimum potential
• Terminal amine in side chain may be primary, secondary and
tertiary as it does not interfere with a activity of drug

20. C ) C I N C H O N A A L K A L O I D S

21. Quinine
IUPAC name: -(R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-
yl]methanol
C I N C H O N A A L K A L O I D S

22. Quinidine
IUPAC name :- (S)-(6-Methoxyquinolin-4-yl)[(1S,2R,4S,5R)-5-vinylquinuclidin-2-
yl]
methanol
C I N C H O N A A L K A L O I D S

23. SAR:
 Quinoline nucleus is essential for anti-malarial activity as it can direct
the intercalate into plasmodium DNA.
 In this drug presence of secondary alcoholic group provide a
secondary binding of DNA structure
 In cinchona alkaloids removal of methoxy group from quinoline
nucleus or vinyl group from quinoclidine nucleus does not affect the
biological activity
 In these drug replacement of methoxy group with halo substituent
improve the activity of drug molecule

24. A N A L O G U E S
Halofanthrine
IUPAC name:- 3-(Dibutylamino)-1-[1,3-dichloro-6-(trifluoromethyl)
-9-phenanthryl]-1-propanol

25. 9- AMINOACRIDINE
Quinacrine
6-chloro-2-methoxy-9-[( 1-methyl-4-diethyleamine)-butyl]-amino acridine

26. MODE OF ACTION
 These drug intercalate into plasmodial DNA and inhibit the nucleic acid
synthesis
 It also claim that they interfere with the mitochondrial electron transport
system in plasmodium
SAR
 Acrdine nucleus is essential for antimalerial action but it is less potent as
compaire to quinoline nucleus
 The presence of methoxy substituent at C2 position and chloro substituent at
C6 position are play an important role while anti-malerial activity of drug
molecule
 At C9 position a carbon chain between 2 nitrogen atom should be consist of
4-6 carbons as it is essential for optimum drug potential
 In side chain, terminal amino should be tertiary. Its replacement with primary
or secondary amino effect of biological activity

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