1. SOLUTION TO MALARIA CHLOROQUINE I CHOICED CHLOROQUINE DUE TO ITS: LIMITED SITE EFFECTS, MORE ACTIVE AND MOEROVER VERY CHEAP

2. HOW IS CHLOROQUINE SYNTHESISED? Chloroquine is an antimalaria drug which is manufactured by the Surry and the Hammar process consisting of the following steps: 1.The condensation of m-chloroaniline with ethyloxaloacetate this reaction takes place at very low temperature and high pressure. 2. The pyrolytic cyclization, saponification, thermal decarboxylation and reaction with phosphorus oxychloride gives 4,7- dichloroquinoline(IV), which is finally condensed with 4-diethylamino-1-methylamino.

3. The yields from this excellent synthesis leaves little to be desired except for the cyclization step, (ii-iii), in which the ring closes partly into the position ortho to the chloro-group giving a mixture containing about 50% of the undesired 5-chloro-isomer. In view of the more specific orientation, in the cyclization of the acid (VI) to give exclusively the desired 7-chloro isomer in over 80% yields. It is consider desirable to investigate the possibility of converting 4-keto-7-chloro-1,2,3,4- tetrahydroquinoline(VII) into chloroquine.

5. MODEL:- IN VITRO TEST OF THE EFFECT OF CHLOROQUINE Collection of P. falciparum: Materials and Methods; 1ml of blood is collected by venipuncture into sterile EDTA tube. Thick and thin blood films are made and stained with 4% Giemsa’s stain for 20min. Parasitaemiaa is quantified per 200 white blood cells on a thick film and expressed as parasites/ul. A slide is considered negative if examination of atleast 200 oil immersion fields reveals no parasite.

6. Procedure:- -Thick and thin blood films are prepared from the blood collected from each subject for parasite identification. -A prepared 50ul of chloroquine concentration is then added to every microlitre plate. -The microlitre plate is placed in a candle jar so as to maintain a relatively high CO2 and low O2 concentration. -The jar is then incubated at 37 degrees celsius(+or- 0.5) for 24-34hr.

7. Results: After incubation, the slide were then air-dried stained for 20min and examined by the use of the light microscope. The blood film was observed under X100 oil immersion objective. The parasite containing slides were observed to be 80% parasite diminished. Conclusion: Chloroquine destroyed the parasite cells within the blood films. AN INVITRO TEST WAS ALSO PERFORMED AND ALMOST THESAME RESULTS WERE OBTAINED.

8. Problem: Why only 80% of the Parasite Were Destroyed? Some of the P. falciparum are resistant to chloroquine SO WHAT CAN BE DONE! SEE IN THE NEXT PRESENTATION…….

9. References Brasseur P, Guiguemde R, Diallo S, Guiyedi V, Kombila M, Ringwald, P, Olliaro P (1999). Amodiaquine remains effective for treating uncomplicated malaria in West and Central Africa. Trans Roy.Soc.Trop. Med. Hyg. 93: 645 - 650. Salako LA, Aderounmu AF (1987). In vitro chloroquine and mefloquine resistant plasmodium falciparum in Nigeria. Lancet ii: 572-573. Spencer HC, Kipinger T, Agure R, Koech DK, Chulay JD (1983). Plasmodium falciparum in Kisumu, Kenya: Differences in sensitivity to Amodiaquine and Chloroquine in-vitro. J. Infectious Dis. 148 (4): 732-736.