MY PROBLEM:-PARASITE RESISTANCE TO CHLOROQUINE Chloroquine has been discovered resistant to the malaria parasite. The reasons for the emergences of resistance are multi-factorial: uncontrolled long-term treatment regimes, travel activity resulting in spread of resistant strains and frequent feeding of mosquitoes from several different hosts. High rate of resistance has been recorded in sub-Sahara Africa countries like Rwanda and Ethiopia.

Modifications to Improve Chloroquine. Chloroquine, 2 contains a 7-chloroquinoline-substituted ring system with a flexible pentadiamino side chain. The haem-binding template, 7-chloro- and terminal amino group are all important for antimalarial activity. Since Amodiaquine retains antimalarial activity against many chloroquine-resistant parasites, the next focus was to make a safer, cost-effective alternative. Initial studies involved the design and synthesis of fluoroamodiaquine since this analogue cannot form toxic metabolites by P450-mediated processes and retains substantial antimalarial activity versus chloroquine-resistant parasites. However, the resulting N-desethyl 40-fluoro amodiaquine metabolite has significantly reduced activity against chloroquine-resistant parasites

- Concerns about cost led to the preparation of other synthetically accessible analogues; the tebuquine series. -Tebuquine (18), an analogue of amodiaquine discovered by Parke-Davis, is significantly more active than amodiaquine and chloroquine both in vitro and in vivo and has potent antimalarial activity and reduced cross-resistance with chloroquine. -Compounds in the tebuquine series have also been shown to have an unacceptable toxicity profile that is aggravated by the long half-lives.

CONCLUSION With this, chloroquine is still an essential drug for the treatment of malaria. Cuz its can still treat about 80% of malaria infection. Just about 20% of it is resistance to the infection. Chloroquine has been the most efficient antimalaria drug for decades and recently, the parasite shows some resistances to it. This has brought fort the idea of modifying the chloroquine to obtain a more efficient analogue form of chloroquine which can act better than chloroquine on the parasite. To conclude, chloroquine remains the backbone for malaria treatment.