9-aminoacridinesAntimalarial drugs

Acridines• Aacridine is formed when an additional benzene ring

is fused with pyridine ring of quinoline nucleus. Acridine is overall aromatic, though having nitrogen

Quinoline Benzene

Pyridine

9-Amino acridine• has an amino group at C -9• It is a green fluorescent dye • In the past, the compound was used as an

antiseptic for treating wounds infections

Structure Activity Relationship• Various types of acridines were synthesized• Acridine has weak antiseptic and antibacterial

activity• When a side chain – 2 amino, 5 diethylamino

pentane- is introduced at C-9, the compound becomes antimalarial

• When methoxy at position 2 and Cl at 6 are introduced –quinacrine- which is antimalarial

• Quinacrine was the 1st synthetic agent that was used before quinolines

Quinacrine

2

9

6

• When methoxy is shifted to position 6 and Cl to 2 (interchanged)-loss of antimalarial activity

• When methoxy is replaced by ethoxy, toxicity is increased

• When methoxy is rotated to any other position 1, 3, 4, then 50% activity is lost

• When Cl is replaced with other halogens there is successive loss of activity

• Side chain – 2 amino, 5 diethylamino pentane- has no antimalarial activity but when attached to aromatic system the compound became antimalarial

• When at position-1, a N is introduced –azacrine- which has good antimalarial activity and rapid onset of action

Azacrine

• A very useful drug was taken from quinacrine by Gemans by separating it into two halves;

• 1 half chloroquine active• 2 half was inactive

Chemical synthesis

Condensation reaction

2, 4 dichloro benzoic acid(p-methoxy aniline)

-HCl

2, p-methoxy phenyl amino, 4 chloro benzoic acid

POCl3

6- chloro , 2-methoxy acredinone

POCl3

6, 9 dichloro, 2-methoxy acredine

6 chloro, 9 diethylaminopentyl, 2-methoxy, acredine

2

Therapeutic uses

• Treating erythrocytic stage of malaria• Earlier, was used in treating black water fever• Have anthalmentic activity against intestinal

parasites• It is eliminated slowly and have side effects

Non-therapeutic use

• Being green fluorescent dye, used to visualize blood cells, particularly platelets

• Platelets store the dye in dense granules

Side effects

• Gastric irritation• Staining of tongue and skin